基于T细胞表位肽的树突细胞介导的靶向性细胞杀伤机制的研究
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摘要
随着免疫识别理论、分子生物学知识和电子显微技术的不断进展与突破,大量研究证实发现T细胞对于抗原的识别是与MHC分子结合递呈的抗原短肽。有效的抗原表位肽可以通过树突细胞呈递到MHC-Ⅰ/MHC-Ⅱ途径引起机体的免疫反应。近年来又有科学家提出复合表位或改构表位可以增强单表位的功能。随着DC疫苗在临床的应用及其相关研究的进一步深入,寻找有效的T细胞表位以增强DC疫苗在抗肿瘤及治疗感染性疾病的作用受到越来越多的重视。如何使外来抗原通过MHC-Ⅰ途径诱发CD8+CTL反应是DC在临床应用中的关键。
该课题的设计主要针对病因明确的病毒性疾病,拟选择以乙型肝炎病毒源性肝炎为疾病模型,以细胞免疫所攻击的乙型肝炎病毒核心蛋白为靶蛋白,通过软件预测的方法分析该蛋白的生物学特性及T细胞表位肽,将设计得到的表位修饰并合成。建立可标准化的DC培养平台;通过实验探讨表位肽对DC功能的影响以及其作用机理,为DC在临床的应用奠定基础。实验分为四部分,具体如下:
第一部分T细胞表位肽的设计与筛选
目的预测HBV核心蛋白的一般生物学特性及该蛋白片段上有效的HLA-2限制性CTL表位。方法从Genebank中选择B型(adw) HBV的核心蛋白,用软件CLC Protein Workbench3版本和SignalP3.0软件(http://www.cbs.dtu.dk/services/SignalP-2.0/)对HBV核心抗原的编码蛋白质进行预测的一般生物学特性;采用SYFPEITHI远程预测数据库、PREDEPP数据库、基序法和多项式法共同对HBV核心抗原编码蛋白进行HLA-A2限制性CTL表位预测。结果通过软件对HBV核心蛋白进行分析,明确了该蛋白质的跨膜区,信号肽,亚细胞定位,抗原性位点。筛选了5条T细胞表位肽。结论预测方案的联合使用可以提高T细胞表位肽筛选的准确率。
第二部分T细胞表位肽的鉴定、修饰与合成
目的鉴定筛选出的5条肽生物学特性,修饰并合成与抗原结合性能最好的肽,为进一步探讨外源性小分子表位肽进入细胞内激发MHC1类反应奠定基础。方法用抗原性能结合实验分别从亲和力、结合稳定性和MHC-肽复合体稳定性三方面鉴定5条表位肽与抗原的结合性能,筛选出结合性能最好的两条肽,并用辅助性T细胞表位、B细胞表位和棕榈酰基修饰,Fmoc方案合成。结果筛选出2条T细胞表位肽,合成9条肽,构成11组表位肽。结论利用抗原结合性能实验和Fmoc合成方案可以完成抗原肽的鉴定与合成。
第三部分人外周血单核细胞来源的树突细胞转化平台的搭建
目的建立一种可标准化、规模操作DC培养、转化及鉴定平台。方法将人外周血的PBMC用CD14+磁珠标记,在磁场中分离出CD14+PBMC;将分选得到的细胞在DC培养袋中加入IL-4,GM-CSF共培养,第10天,收集细胞计数,Typanlan染色观察活性,流式细胞仪检测细胞表型,扫描电镜观察细胞形态。结果光学显微镜下,树突状细胞悬浮生长,大小不等,形态极不规则,向四周伸出不同数量的粗细不一、形态迥异的胞质突起。CD14+PBMC在初始血液中的比例为14%,而经过分离纯化后的CD14+细胞的浓度达到94.8%。在培养10天后的细胞悬液中,由于大部分细胞转化为DC,所以分子表面标志发生改变,CD14+细胞的浓度仅为0.65%;在培养出的DC细胞表面高表达HLA-I(70.43%),HLA-Dr(0.65%),CD80(89.45% ),CD86(86.32%),部分表达CD40(29.61%)。这些细胞表面分子标志都是人PBMC转化为DC后的特征性分子。扫描电镜可见被固定的树突状细胞仍保持其特征性的突起,使细胞呈星状、多角形或极不规则形。突起长短不一,分支形成1-4级的亚突起。结论从PBMC中分离纯化的CD14+细胞通过加入细胞因子可以在细胞培养袋中非贴壁式培养出高纯度的DC。
第四部分DC介导的靶向性杀伤功能及机制的初步探讨
目的对比负载不同表位肽的DC的生物学功能筛选出杀伤功能最佳的表位肽组合,从微分子水平探讨组合肽的功能性差异。方法用四噻唑蓝法实验检测细胞毒功能;ELISPOT实验检测负载不同表位的DC刺激T细胞分泌γ-IFN的功能;原子力显微镜分析DC经小分子肽作用后表面精细结构改变;激光共聚焦显微镜分析小分子肽进入细胞后不同时间的表现;免疫荧光显微镜观察DC摄取肽的过程。结果细胞经第T1,T1+T2,T1+Th,T1-AAA-Th,pal-KSST1,pal-KSST1AAATh,T1+B,pal-KSST1Th,T1+Th,B组短肽处理后,细胞活性较对照组有显著性升高(p<0.05),其中第T1+B组肽则可使细胞活性呈现极显著升高(p<0.01),而经T2,Th,T1Th短肽处理后,细胞活性较对照组有显著性降低(p<0.05),其中第T2组肽使细胞活性呈现极显著降低。筛选出的表位肽T1可以上调DC对T细胞刺激能力(P<0.01),而经过棕榈酰丝氨酸修饰的表位或B细胞、Th协同的T细胞表位负载DC刺激能力也有同样表现(P<0.01),无论辅助性T细胞表位还是B细胞表位对于T1均有协同作用。将辅助性T细胞表位直接偶联到T1表位上,破坏了T1刺激DC的能力。即使在T1表位和Th内部通过AAA连接,并以棕榈酰丝氨酸修饰也不会表现出比单独的T1表位明显的功能增强。激光共聚焦的结果显示小分子肽可以在30分钟被DC快速摄取,免疫荧光显微镜发现肽的摄取是在5min内完成的;小分子肽的摄取由胞体完成后向树突传递,而且树突的肽浓度相对胞体较低。小分子肽被细胞摄取后的12h内,始终不曾进入细胞核。在透射电镜下,负载肽的DC线粒体增大,增多,核糖体和内质网丰富。而MTT活性检测实验显示这些被肽激活的DC的功能上调。结论DC经不同短肽处理后,细胞活性会产生一定程度的改变。短肽使T淋巴细胞的杀伤活性增高的原因主要是通过DC激活了细胞免疫途径,发挥了CTL效应。棕榈酰基修饰后可以上调T细胞表位的功能;B细胞表位和Th可以通过表位间的协同作用增强T细胞表位肽激活CTL的效应。AFM观察到细胞表面形貌变化受外源性小分子肽一级结构的影响,而且直接影响细胞的活性。小分子肽不作为遗传物质参与细胞的信息传递,这一现象为表位肽作为疫苗,与DC共培养后回输机体的安全性提供了理论基础。
研究发现软件预测是一种可行的T细胞表位肽筛选方案,极大的缩减了实验的工作量,不同类别的表位肽之间的协同作用对于上调DC的生物学功能大于表位间的偶联效应。棕榈酰化表位肽也可以上调DC对于T细胞的刺激能力。不同的小分子肽对DC表面的精细结构的影响不一样,产生的CTL杀伤效应也不同。
With the development of immunology, molecular biology, and micro-electronics technology, insights regarding peptide binding with major histocompatability complex (MHC) molecules have revealed a vital role in recognition between T cell and antigen. Antigen epitope can be presented on MHC-Ⅰor II molecules by antigen presenting cells and promote an immune response. Recently, the theory that both was considered that both compound-epitopes and modified epitopes can be more effective at enhancing the function of cytotoxic lymphocytes (CTL) was proposed. Therefore, attention has focused on finding efficient epitopes that upregulate the function of dendritic cells (DC) for treating cancer and infectious diseases. It is key for the application of DC therapy in clinic to determine how to best induce CD8+CTL through MHC-I by exogenous peptides.
Our research is focused on the treatment of hepatitis B virus (HBV). The HBV core protein was selected as the antigen source for presentation by DC. The HBV core protein was analysed by specialized software. Biological characteristics of HBV core protein were acquired. T epitopes were analyzed, modified and synthesized. A DC culturing platform was established and standardized. Experiments were designed to elucidate the function and mechanism of peptide-pulsed-DC.
Specific Aim I: Screening of T Epitopes
Objective. To predict the characteristics of efficient T epitopes restricted by HLA-A2 of the HBV core protein. Methods. B type(adw subtype) HBV core protein from Genebank was selected and predicted normal characteristics by CLC Protein Workbench3 version and SignalP3.0 software(http://www.cbs.dtu.dk/services/SignalP-2.0/)and T epitopes restricted by HLA-A2 by SYFPEITHI databank, PREDEEP databank, matrix. Results. The cross-membrane region, signal peptides, and antigenic sites of HBV core protein were identified and five T epitopes were selected for analysis. Conclusion. Combining several prediction methods can boost the prediction accuracy of T epitopes.
Specific Aim II: Identifying, Modifying, and Synthesizing T Epitopes
Objective. To Identify, modify, and synthesize five peptides for elucidating the mechanism of exogenous peptides entering DC by the MHC I pathway. Methods. Antigen binding experiments were performed to identify affinities, binding affinities, and MHC-peptide complex stability of five epitopes. Two peptides with the best performance were selected, modified with Th, B, and palmitoyl, then synthesized. Results. Two peptides were acquired, and nine peptides were synthesized and eleven epitopes were obtained. Conclusion. Antigen binding experiments with the Fmoc synthesis method can be used to identify and synthesize epitopes.
Specific Aim III: Establishing a Platform of DC Generation
Objective. To establish a reproducible, large-scale platform to generate DC. Methods. Human peripheral blood mononuclear cells (PBMC) were labeled with CD14+ magnetic beads. CD14+ cells were isolated and cultured with IL-4 and GM-CSF in a culture bag for ten days, then harvested. The viability of DC was determined by Typanlan staining. DC phenotype was determined by FACS. The morphology of these DC was observed under a scanning electron microscope. Results. DC suspended in culture medium result in variable cell size and irregular morphology. Cytoplasmic dendrites were extended. 14% of PBMC are CD14+. Magnetic bead purification of PBMC resulted in 94.8% purity of CD14+ cells. After ten days of culture, the majority of PBMC expressed a DC phenotype with only 0.65% of cells expressing CD14. Certain cell surface molecules were expressed at ten days including HLA-I (70.43%),HLA-Dr (0.65%),CD80 (89.45%),CD86 (86.32%), and CD40 (29.61%). By electron microscopy, DC retained their specific morphology. Conclusion. CD14+ cells isolated from PBMC can be non-adherently cultured and transformed into pure DC in culture bags.
Specific Aim IV: The Function and Mechanism of Peptide-Pulsed DC
Objective. To compare the biological functions of DC loaded with different epitopes and select the peptide that results in the most effective CTL response. To investigate functional differences in DC pulsed with different peptides. Methods. The cytotoxity of T cells was tested by MTT assay and the amount of secretion ofγ-IFN was detected by ELISPOT. Fine structures on the DC surface loaded with different peptides were observed under atomic force microscope(AFM). The behavior of peptides in the DC at different time points were analyzed by laser scanning confocal microscope (LSCM). Results. The function of DC are upregulated when they were pulsed by peptide through MTT assay. Cell viability was significantly higher(p<0.05)when they were pulsed with T1,T1+T2,T1+Th,T1-AAA-Th,pal-KSST1,pal-KSST1AAATh,pal-KSST1Th,T1+B,T1+Th,B epitopes and especially by T1+B epitope(p<0.01). However, cell viability was significantly lower when treated with T2,Th,T1Th, and was at its lowest when treated with T2 epitope. T1 can upregulate DC function (p<0.01). T epitopes all show higher activity when they are modified by B epitope, helper T cell, and palmitoyl(p<0.01=. The results of the laser scanning confocal microscope demonstrated that small peptides can be taken up within 30 minutes by DC and transfer to branches from the cytoplasm. However, the concentration of peptide is lower in the branches than in the cell body. Peptide never was able to enter the nuclear within 12 hours in our experiment. Under TEM, peptide-pulsed DC display larger and a greater number of mitochondria in the cytoplasm. Ribosomes and endoplasmic reticulum are abundant. Conclusion. Viability of DC can change when they are treated with peptides. The reason that the epitope increased the CTL response is that exogenous peptide can induce a cellular response through the cross-presenting pathway of MHC I and promote the CTL reaction. DC function can be upregulated by epitope modified by palmitol B epitope. Both Th epitope and B epitope all have synergistic effect on T epitopes. Even if three alanine were linked between them and palmitoyl were joined to the N-terminal, the epitope did not induce an antigen-specific T cell reaction differently compared to T1 epitope. However, the way peptides entered into dendritic cell were changed. Cell-surface DC morphology changes when DC were loaded with different protein sequence under AFM. Fine structures on the surface of DC have a strong relationship with viability. Small peptides can upregulate DC function but cannot alter genetic information transmission. Small peptide still enter the cell through the endosome/lysosome pathway and are presented by MHC I on the cell surface.
In our investigation, it is feasible to predict T epitopes by software, which greatly reduces conventional workload. Small peptides are taken up by DC through endocytosis. Different epitopes have different effects on DC in a CTL reaction, fine structures on the cell surface, and the function of DC. This finding suggests that small peptides do not directly participate in genetic information transmission when DC are loaded with peptides. Our research provides evidence that peptide-pulsed DC may be employed therapeutically in clinic.
该课题的设计主要针对病因明确的病毒性疾病,拟选择以乙型肝炎病毒源性肝炎为疾病模型,以细胞免疫所攻击的乙型肝炎病毒核心蛋白为靶蛋白,通过软件预测的方法分析该蛋白的生物学特性及T细胞表位肽,将设计得到的表位修饰并合成。建立可标准化的DC培养平台;通过实验探讨表位肽对DC功能的影响以及其作用机理,为DC在临床的应用奠定基础。实验分为四部分,具体如下:
第一部分T细胞表位肽的设计与筛选
目的预测HBV核心蛋白的一般生物学特性及该蛋白片段上有效的HLA-2限制性CTL表位。方法从Genebank中选择B型(adw) HBV的核心蛋白,用软件CLC Protein Workbench3版本和SignalP3.0软件(http://www.cbs.dtu.dk/services/SignalP-2.0/)对HBV核心抗原的编码蛋白质进行预测的一般生物学特性;采用SYFPEITHI远程预测数据库、PREDEPP数据库、基序法和多项式法共同对HBV核心抗原编码蛋白进行HLA-A2限制性CTL表位预测。结果通过软件对HBV核心蛋白进行分析,明确了该蛋白质的跨膜区,信号肽,亚细胞定位,抗原性位点。筛选了5条T细胞表位肽。结论预测方案的联合使用可以提高T细胞表位肽筛选的准确率。
第二部分T细胞表位肽的鉴定、修饰与合成
目的鉴定筛选出的5条肽生物学特性,修饰并合成与抗原结合性能最好的肽,为进一步探讨外源性小分子表位肽进入细胞内激发MHC1类反应奠定基础。方法用抗原性能结合实验分别从亲和力、结合稳定性和MHC-肽复合体稳定性三方面鉴定5条表位肽与抗原的结合性能,筛选出结合性能最好的两条肽,并用辅助性T细胞表位、B细胞表位和棕榈酰基修饰,Fmoc方案合成。结果筛选出2条T细胞表位肽,合成9条肽,构成11组表位肽。结论利用抗原结合性能实验和Fmoc合成方案可以完成抗原肽的鉴定与合成。
第三部分人外周血单核细胞来源的树突细胞转化平台的搭建
目的建立一种可标准化、规模操作DC培养、转化及鉴定平台。方法将人外周血的PBMC用CD14+磁珠标记,在磁场中分离出CD14+PBMC;将分选得到的细胞在DC培养袋中加入IL-4,GM-CSF共培养,第10天,收集细胞计数,Typanlan染色观察活性,流式细胞仪检测细胞表型,扫描电镜观察细胞形态。结果光学显微镜下,树突状细胞悬浮生长,大小不等,形态极不规则,向四周伸出不同数量的粗细不一、形态迥异的胞质突起。CD14+PBMC在初始血液中的比例为14%,而经过分离纯化后的CD14+细胞的浓度达到94.8%。在培养10天后的细胞悬液中,由于大部分细胞转化为DC,所以分子表面标志发生改变,CD14+细胞的浓度仅为0.65%;在培养出的DC细胞表面高表达HLA-I(70.43%),HLA-Dr(0.65%),CD80(89.45% ),CD86(86.32%),部分表达CD40(29.61%)。这些细胞表面分子标志都是人PBMC转化为DC后的特征性分子。扫描电镜可见被固定的树突状细胞仍保持其特征性的突起,使细胞呈星状、多角形或极不规则形。突起长短不一,分支形成1-4级的亚突起。结论从PBMC中分离纯化的CD14+细胞通过加入细胞因子可以在细胞培养袋中非贴壁式培养出高纯度的DC。
第四部分DC介导的靶向性杀伤功能及机制的初步探讨
目的对比负载不同表位肽的DC的生物学功能筛选出杀伤功能最佳的表位肽组合,从微分子水平探讨组合肽的功能性差异。方法用四噻唑蓝法实验检测细胞毒功能;ELISPOT实验检测负载不同表位的DC刺激T细胞分泌γ-IFN的功能;原子力显微镜分析DC经小分子肽作用后表面精细结构改变;激光共聚焦显微镜分析小分子肽进入细胞后不同时间的表现;免疫荧光显微镜观察DC摄取肽的过程。结果细胞经第T1,T1+T2,T1+Th,T1-AAA-Th,pal-KSST1,pal-KSST1AAATh,T1+B,pal-KSST1Th,T1+Th,B组短肽处理后,细胞活性较对照组有显著性升高(p<0.05),其中第T1+B组肽则可使细胞活性呈现极显著升高(p<0.01),而经T2,Th,T1Th短肽处理后,细胞活性较对照组有显著性降低(p<0.05),其中第T2组肽使细胞活性呈现极显著降低。筛选出的表位肽T1可以上调DC对T细胞刺激能力(P<0.01),而经过棕榈酰丝氨酸修饰的表位或B细胞、Th协同的T细胞表位负载DC刺激能力也有同样表现(P<0.01),无论辅助性T细胞表位还是B细胞表位对于T1均有协同作用。将辅助性T细胞表位直接偶联到T1表位上,破坏了T1刺激DC的能力。即使在T1表位和Th内部通过AAA连接,并以棕榈酰丝氨酸修饰也不会表现出比单独的T1表位明显的功能增强。激光共聚焦的结果显示小分子肽可以在30分钟被DC快速摄取,免疫荧光显微镜发现肽的摄取是在5min内完成的;小分子肽的摄取由胞体完成后向树突传递,而且树突的肽浓度相对胞体较低。小分子肽被细胞摄取后的12h内,始终不曾进入细胞核。在透射电镜下,负载肽的DC线粒体增大,增多,核糖体和内质网丰富。而MTT活性检测实验显示这些被肽激活的DC的功能上调。结论DC经不同短肽处理后,细胞活性会产生一定程度的改变。短肽使T淋巴细胞的杀伤活性增高的原因主要是通过DC激活了细胞免疫途径,发挥了CTL效应。棕榈酰基修饰后可以上调T细胞表位的功能;B细胞表位和Th可以通过表位间的协同作用增强T细胞表位肽激活CTL的效应。AFM观察到细胞表面形貌变化受外源性小分子肽一级结构的影响,而且直接影响细胞的活性。小分子肽不作为遗传物质参与细胞的信息传递,这一现象为表位肽作为疫苗,与DC共培养后回输机体的安全性提供了理论基础。
研究发现软件预测是一种可行的T细胞表位肽筛选方案,极大的缩减了实验的工作量,不同类别的表位肽之间的协同作用对于上调DC的生物学功能大于表位间的偶联效应。棕榈酰化表位肽也可以上调DC对于T细胞的刺激能力。不同的小分子肽对DC表面的精细结构的影响不一样,产生的CTL杀伤效应也不同。
With the development of immunology, molecular biology, and micro-electronics technology, insights regarding peptide binding with major histocompatability complex (MHC) molecules have revealed a vital role in recognition between T cell and antigen. Antigen epitope can be presented on MHC-Ⅰor II molecules by antigen presenting cells and promote an immune response. Recently, the theory that both was considered that both compound-epitopes and modified epitopes can be more effective at enhancing the function of cytotoxic lymphocytes (CTL) was proposed. Therefore, attention has focused on finding efficient epitopes that upregulate the function of dendritic cells (DC) for treating cancer and infectious diseases. It is key for the application of DC therapy in clinic to determine how to best induce CD8+CTL through MHC-I by exogenous peptides.
Our research is focused on the treatment of hepatitis B virus (HBV). The HBV core protein was selected as the antigen source for presentation by DC. The HBV core protein was analysed by specialized software. Biological characteristics of HBV core protein were acquired. T epitopes were analyzed, modified and synthesized. A DC culturing platform was established and standardized. Experiments were designed to elucidate the function and mechanism of peptide-pulsed-DC.
Specific Aim I: Screening of T Epitopes
Objective. To predict the characteristics of efficient T epitopes restricted by HLA-A2 of the HBV core protein. Methods. B type(adw subtype) HBV core protein from Genebank was selected and predicted normal characteristics by CLC Protein Workbench3 version and SignalP3.0 software(http://www.cbs.dtu.dk/services/SignalP-2.0/)and T epitopes restricted by HLA-A2 by SYFPEITHI databank, PREDEEP databank, matrix. Results. The cross-membrane region, signal peptides, and antigenic sites of HBV core protein were identified and five T epitopes were selected for analysis. Conclusion. Combining several prediction methods can boost the prediction accuracy of T epitopes.
Specific Aim II: Identifying, Modifying, and Synthesizing T Epitopes
Objective. To Identify, modify, and synthesize five peptides for elucidating the mechanism of exogenous peptides entering DC by the MHC I pathway. Methods. Antigen binding experiments were performed to identify affinities, binding affinities, and MHC-peptide complex stability of five epitopes. Two peptides with the best performance were selected, modified with Th, B, and palmitoyl, then synthesized. Results. Two peptides were acquired, and nine peptides were synthesized and eleven epitopes were obtained. Conclusion. Antigen binding experiments with the Fmoc synthesis method can be used to identify and synthesize epitopes.
Specific Aim III: Establishing a Platform of DC Generation
Objective. To establish a reproducible, large-scale platform to generate DC. Methods. Human peripheral blood mononuclear cells (PBMC) were labeled with CD14+ magnetic beads. CD14+ cells were isolated and cultured with IL-4 and GM-CSF in a culture bag for ten days, then harvested. The viability of DC was determined by Typanlan staining. DC phenotype was determined by FACS. The morphology of these DC was observed under a scanning electron microscope. Results. DC suspended in culture medium result in variable cell size and irregular morphology. Cytoplasmic dendrites were extended. 14% of PBMC are CD14+. Magnetic bead purification of PBMC resulted in 94.8% purity of CD14+ cells. After ten days of culture, the majority of PBMC expressed a DC phenotype with only 0.65% of cells expressing CD14. Certain cell surface molecules were expressed at ten days including HLA-I (70.43%),HLA-Dr (0.65%),CD80 (89.45%),CD86 (86.32%), and CD40 (29.61%). By electron microscopy, DC retained their specific morphology. Conclusion. CD14+ cells isolated from PBMC can be non-adherently cultured and transformed into pure DC in culture bags.
Specific Aim IV: The Function and Mechanism of Peptide-Pulsed DC
Objective. To compare the biological functions of DC loaded with different epitopes and select the peptide that results in the most effective CTL response. To investigate functional differences in DC pulsed with different peptides. Methods. The cytotoxity of T cells was tested by MTT assay and the amount of secretion ofγ-IFN was detected by ELISPOT. Fine structures on the DC surface loaded with different peptides were observed under atomic force microscope(AFM). The behavior of peptides in the DC at different time points were analyzed by laser scanning confocal microscope (LSCM). Results. The function of DC are upregulated when they were pulsed by peptide through MTT assay. Cell viability was significantly higher(p<0.05)when they were pulsed with T1,T1+T2,T1+Th,T1-AAA-Th,pal-KSST1,pal-KSST1AAATh,pal-KSST1Th,T1+B,T1+Th,B epitopes and especially by T1+B epitope(p<0.01). However, cell viability was significantly lower when treated with T2,Th,T1Th, and was at its lowest when treated with T2 epitope. T1 can upregulate DC function (p<0.01). T epitopes all show higher activity when they are modified by B epitope, helper T cell, and palmitoyl(p<0.01=. The results of the laser scanning confocal microscope demonstrated that small peptides can be taken up within 30 minutes by DC and transfer to branches from the cytoplasm. However, the concentration of peptide is lower in the branches than in the cell body. Peptide never was able to enter the nuclear within 12 hours in our experiment. Under TEM, peptide-pulsed DC display larger and a greater number of mitochondria in the cytoplasm. Ribosomes and endoplasmic reticulum are abundant. Conclusion. Viability of DC can change when they are treated with peptides. The reason that the epitope increased the CTL response is that exogenous peptide can induce a cellular response through the cross-presenting pathway of MHC I and promote the CTL reaction. DC function can be upregulated by epitope modified by palmitol B epitope. Both Th epitope and B epitope all have synergistic effect on T epitopes. Even if three alanine were linked between them and palmitoyl were joined to the N-terminal, the epitope did not induce an antigen-specific T cell reaction differently compared to T1 epitope. However, the way peptides entered into dendritic cell were changed. Cell-surface DC morphology changes when DC were loaded with different protein sequence under AFM. Fine structures on the surface of DC have a strong relationship with viability. Small peptides can upregulate DC function but cannot alter genetic information transmission. Small peptide still enter the cell through the endosome/lysosome pathway and are presented by MHC I on the cell surface.
In our investigation, it is feasible to predict T epitopes by software, which greatly reduces conventional workload. Small peptides are taken up by DC through endocytosis. Different epitopes have different effects on DC in a CTL reaction, fine structures on the cell surface, and the function of DC. This finding suggests that small peptides do not directly participate in genetic information transmission when DC are loaded with peptides. Our research provides evidence that peptide-pulsed DC may be employed therapeutically in clinic.
引文
1. Maurer K, Harrer EG, Goldwich A, Eismann K, Bergmann S, Schmitt-Haendle M, Spriewald B, Mueller SM, Harrer T. Role of Cytotoxic T-Lymphocyte-Mediated Immune Selection in a Dominant Human Leukocyte Antigen-B8-Restricted Cytotoxic T-Lymphocyte Epitope in Nef. J Acquir Immune Defic Syndr, 2008 [Epub ahead of print]
2. Chentoufi AA, Zhang X, Lamberth K, Dasgupta G, Bettahi I, Nguyen A, Wu M, Zhu X, Mohebbi A, Buus S, Wechsler SL, Nesburn AB, Benmohamed L. HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D. J Immunol, 2008, 180(1):426-37
3. Sidney J, Assarsson E, Moore C, Ngo S, Pinilla C, Sette A, Peters B. Quantitative peptide binding motifs for 19 human and mouse MHC class I molecules derived using positional scanning combinatorial peptide libraries. Immunome Res, 2008, 25(4):2
4. Mirano-Bascos D, Tary-Lehmann M, Landry SJ. Antigen structure influences helper T-cell epitope dominance in the human immune response to HIV envelope glycoprotein gp120. Eur J Immunol. 2008[Epub ahead of print]
5. Wilson CC, Newman MJ, Livingston BD, Mawhinney S, Forster JE, Scott J, Schooley RT, Benson CA. Clinical Phase 1 Safety and Immunogenicity Testing of an Epitope-based DNA Vaccine in HIV-1-infected Subjects Receiving Highly Active Antiretroviral Therapy (HAART). Clin Vaccine Immunol, 2008[Epub ahead of print]
6. Jarchum I, Nichol L, Trucco M, Santamaria P, Dilorenzo TP. Identification of novel IGRP epitopes targeted in type 1 diabetes patients. Clin Immunol, 2008 ,19[Epub ahead of print]
7. Han N, J?rvinen KM, Cocco RR, Busse PJ, Sampson HA, Beyer K. Identification of amino acids critical for IgE-binding to sequential epitopes of bovine kappa-casein and the similarity of these epitopes to the corresponding human kappa-casein sequence.
8. Wilkinson RA, Evans JR, Jacobs JM, Slunaker D, Pincus SH, Pinter A, Parkos CA, Burritt JB, Teintze M. Peptides selected from a phage display library with an HIV-neutralizing antibody elicit antibodies to HIV gp120 in rabbits, but not to the same epitope. AIDS Res Hum Retroviruses. 2007, 23(11):1416-279
9. Fagerberg T, Cerottini JC, Michielin O. Structural prediction of peptides bound to MHC class I.J Mol Biol, 2006 , 356(2):521-46
10. Nishikawa M, Takemoto S, Takakura Y. Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm, 2008, 1354(1-2):23-7.
11. Okochi M, Hayashi H, Ito A, Kato R, Tamura Y, Sato N, Honda H. Identification of HLA-A24-restricted epitopes with high affinities to Hsp70 using peptide arrays. J Biosci Bioeng, 2008, 105(3):198-203
12. Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol, 2008, 9(1):8
13. Ge Q, Holler PD, Mahajan VS, Nuygen T, Eisen HN, Chen J. Development of CD4+ T cells expressing a nominally MHC class I-restricted T cell receptor by two different mechanisms. Proc Natl Acad Sci U S A, 2006, 103(6):1822-7.
14. Mishto M, Luciani F, Holzhütter HG, Bellavista E, Santoro A, Textoris-Taube K, Franceschi C, Kloetzel PM, Zaikin A. Modeling the in vitro 20S proteasome activity: the effect of PA28-alphabeta and of the sequence and length of polypeptides on the degradation kinetics. J Mol Biol, 2008, 377(5):1607-17
15. Marcilla M, Villasevil EM, de Castro JA.Tripeptidyl peptidase II is dispensable for the generation of both proteasome-dependent andproteasome-independent ligands of HLA-B27 and other class I molecules. Eur J Immunol, 2008, 38(3):631-9
16. Hwang MS, Kim KN, Lee JH, Park YI. Identification of amino acid sequences determining interaction between the cucumber mosaic virus-encoded 2a polymerase and 3a movement proteins. J Gen Virol, 2007, 88(Pt12):3445-51
17. Saudemont A, Hamrouni A, Marchetti P, Liu J, Jouy N, Hetuin D, Colucci F, Quesnel B. Dormant tumor cells develop cross-resistance to apoptosis induced by CTLs or imatinib mesylate via methylation of suppressor of cytokine signaling 1. Cancer Res, 2007, 67(9):4491-8
18. 支 轶,吴玉章,万瑛. 生物信息学方法在 CTL 表位预测中的应用. 免疫学杂志, 2005, 21(2):155-150
19. 林治华,吴玉章. 计算机辅助 T 细胞表位鉴定. 生命的化学, 2004, 24(5):397-399
20. Zajac P, Oertli D, Spagnoli GC, Noppen C, Schaefer C, Heberer M, Marti WR. Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in vitro stimulation with a replication-incompetent vaccinia virus encoding MART-1/Melan-A 27-35 epitope. Int J Cancer, 1997, 71(3):491-6
21. Sahin U,Tureci O, Pfreundschuh M. Serological identification of human tumor antifens. Curr Opin Immunol, 1997;9:709-16
22. 张立红, 张晓楠, 曲萍, 叶菁, 隋延仿, 郭爱林. 突变的肝细胞生长因子受体被肝癌细胞 HLA-A2 分子递呈的实验研究。中华医学杂志, 2001;81:30-32
23. 郭爱林,张敏,隋延仿. 一个新的 MAGE-1 抗原肽为肝癌细胞表面HLA-B7 分子递呈. 中国免疫学杂志,2001;5(17):527-530
24. Stevanovic S. Identification of tumou-associated T-cell epitopes for vaccine development. Nature Rev, 2002,2:1-7
25. Lucas S, De Smet C, Arden KC, Viars CS, Lethé B, Lurquin C, Boon T. Identification of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res. 1998, 58(4):743-52.
26. Chen L. Mimotopes of cytolytic T lymphocytes in cancer immunotherapy. Curr Opin Immunol, 1999, 11:219-222
27. Tsurui H, Takahashi T. Prediction of T-cell epitope. J Pharmacol Sci, 2007, 105(4):299-316
28. Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol, 2008, 9(1):8
29. Malcherek G, Falk K, R?tzschke O, Rammensee HG, Stevanovi? S, Gnau V, Jung G, Melms A. Natural peptide ligand motifs of two HLA molecules associated with myasthenia gravis. Int Immunol. 1993, 5(10):1229-37
30. Keles S, van der Laan MJ, Vulpe C. Regulatory motif finding by logic regression. Bioinformatics, 2004, 20(16):2799-811
31. Kast WM, Brandt RM, Sidney J, Drijfhout JW, Kubo RT, Grey HM, Melief CJ, Sette A.Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. J Immunol, 1994, 152(8):3904-12
32. Kubo RT, Sette A, Grey HM, Appella E, Sakaguchi K, Zhu NZ, Arnott D, Sherman N, Shabanowitz J, Michel H.Definition of specific peptide motifs for four major HLA—A alleles.J lmmunol 1994,152(9):3913·3925
33. Ruppert J, Sidney J, Celis E, Kubo RT, Grey HM, Sette A.Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929-37
34. Keles S, van der Laan MJ, Vulpe C. Regulatory motif finding by logic regression. Bioinformatics. 2004, 20(16):2799-811
35. 黄健.HLA 超型与表位肽超基序及其理论与现实意义.国外医学免疫学分册 2001,24(6):305-306
36. Altfeld MA, Livingston B,Reshamwala N,et a1.Identification of novel HLA-A2-restricted human immunedeficiency virus type 1-specific cytotoxic T—lymphocyte epitopes predicted by the HLA-A2 supertype peptide-bindingmotif.J Virol, 2001, 75(3):1301-1311
37. Endo D, Kanaho Y, Park MK.Gen Comp Endocrinol. Expression of sex steroid hormone-related genes in the embryo of the leopard gecko. 2008, 155(1):70-8
38. Davenport MP, Ho Shon IA, Hill AV. An empirical method for the prediction of T-cell epitopes. Immunogenetics. 1995, 42(5):392-7
39. Dick TP, Stevanovi? S, Keilholz W, Ruppert T, Koszinowski U, Schild H, Rammensee HG. The making of the dominant MHC class I ligand SYFPEITHI.
40. Gomez-Nunez M, Pinilla-Ibarz J, Dao T, May RJ, Pao M, Jaggi JS, Scheinberg DA. Peptide binding motif predictive algorithms correspond with experimental binding of leukemia vaccine candidate peptides to HLA-A*0201 molecules. Leuk Res. 2006, 30(10):1293-8
41. ParkerKC,Bednarek MA,ColiganJE.Schemefor ranking poten—tim HLA—A2 binding peptides based on independent binding of in—dividual peptide side-chains.J lmmunol, 1994,152(1):l63-175
42. Stryhn A, Pedersen LO, Romme T, Holm CB, Holm A, Buus S. Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding. Eur J Immunol, 1996, 26(8):1911-8.
43. Gulukota K,Sidney J,Sette A。et a1.Two complementary methods for predicting poptides binding major histcompatibilIIy complex molecules. J Mol Biol, 1997, 267(5):1258-1267
44. Dick TP, Stevanovi? S, Keilholz W, Ruppert T, Koszinowski U, Schild H, Rammensee HG. The making of the dominant MHC class I ligandSYFPEITHI. Eur J Immunol. 1998 Aug;28(8):2478-86
45. Reche PA, Glutting JP, Zhang H, Reinherz EL. Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics. 2004 Sep;56(6):405-19
46. Singh H,Raghava GP.Propred I:Prediction of promiscuous MHC class—I binding sites.Bioinformaties, 2003,19(8):l009-l014
47. Marusarz RK, Sayeh MR. Neural network-based multimode fiber-optic information transmission. Appl Opt. 2001, 40(2):219-27.
48. Adams HP, Kodol JA.Prediction of binding to MHC dass I molecules.J Immunol Methods 1995,185(2) 181—190.
49. Bohr H , et al. Protein secondary structure and homology by neural network. FEBS Lett , 1988 , 241 : 171 – 176
50. Wikmington. Use neural network for problem solving. Chem Eng Prog , 1993, 89 (4): 44 – 50
51. Gulukota K, Sidney J, Sette A, DeLisi C. Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J Mol Biol. 1997; 267(5):1258-67
52. Brusie V,Petrovsky N,Zhang G,et a1.Prediction of promiscuous peptides that bind HLA class I molecules.Immunol Cel Biol, 2002, 80(3):280-285.
53. Schonbach C,Kun Y,Brusie V.L 丑 rge—scale COmputational iden·tifieation of HIV T—cell epitopes.Immunol Cell Biol 2002,80(3):300-306.
54. 李孝安, 张晓缋. 神经网络与神经计算导论. 西安: 西北工业大学出版社, 1994. 34 – 36
55. Altuvia Y, Schueler O, Margalit H.Ranking potential binding peptides to MHC molecules by a computational threading approach. J Mol Biol, 1995, 249(2):244-50.
56. Doytchinova IA, Walshe V, Borrow P, Flower DR. Towards thechemometric dissection of peptide--HLA-A*0201 binding affinity: comparison of local and global QSAR models. J Comput Aided Mol Des. 2005, 19(3):203-12
57. Chiang RA, Meng EC, Huang CC, Ferrin TE, Babbitt PC.The Structure Superposition Database. Nucleic Acids Res, 2003, 31(1):505-10.
58. Scherf T, Hiller R, Naider F, Levitt M, Anglister J. Induced peptide conformations in different antibody complexes: molecular modeling of the three-dimensional structure of peptide-antibody complexes using NMR-derived distance restraints. Biochemistry, 1992, 31(30):6884-97
59. Lim JS,Kim S,Lee HG,et a1.Selection ofpeptides that bind to the HLA-A2 . 1 molecule by molecular modeling. Mol Immunol 1996, 33(2):221-230.
60. Altuvia Y,Sehueler 0,Margalit H.Ranking potential binding poptides to MHC molecules by a computational threading approach. J Mol Biol 1995, 249(2):244-250.
61. Altuvia Y,Sette A,Sidney J,et a1.A structure-based algorithm to predict potential binding peptides to MHC molecules with hydrophobie binding pockets. Hum lmmunol, 1997, 58(1):1 一 l1.
62. Sehueler Furman O,Elber R, Margalit H. Knowledge-based structure prediction of MHC class l bound peptides:a study of 23 complexes.Fold Des, 1998, 3(6):549-564.
63. Schueler-Furman O, Altuvia Y, Sette A, Margalit H. Structure based prediction of binding peptides to MHC class I molecules:application to a broad range of MHC allele.Protein Sci, 2000, 9(9):1838—1846
64. Zhang C,Andemon A,Delisi.Structural principles that govern the poptide—binding motifs of class I MHC molecules.J Mol Bid, 1998, 281(5):929-947.
65. Logean A,Rognan D.Recovery of known T-cell epitopes by computational scanning of a viral ganome.J Comput Aided Mol Des, 2002,16(4):229-243
66. Holzhutter HG,Frommel C,Kloetzel PM.A theoretical approach towards the identification of cleavage-determining amino acid motifs ofthe 20 S proteasome.J Mol Biol,1999,286(4):1251—1265.
67. Nussbaum AK, Kuttler C, Hadeler KP, Rammensee HG, Schild H. Nussbaum AK,Kuttler C,Hadeler KP,el a1.PAProC:a prediction algorithm for proteasomal cleavages available on the www.Immunogenetics,2001,53(2):87-94
68. Kesmir C,Nnssbaum AK,Sctnld H.el a1.Prediction of proteasome cleavage motifs by neural networks.Protein Eng,2002,15(4):287-296
69. Duniel S,Brusic V,Caillat.Zucman S.Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules.J Immunol,1998,161(2):617-624.
70. Doytchinova IA,Flower DR.Physicochemical explanation of peptide binding to HLA-A*0201 major histocompatibility complex: a three-dimensional quantitative structure-activity relationship study.Proteins,2002,48 (3):505—518.
71. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovi? S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999 Nov;50(3-4):213-9.
72. Brusic V, Rudy G, Harrison LC. MHCPEP, a database of MHC-binding peptides update 1997. Nucleic Acids Res, 1998, 26:368–71
73. Blythe MJ, Doytchinova IA, Flower DR. JenPep: a database of quantitative functional peptide data for immunology. Bioinformatics. 2002 18:434–9.
74. Schonbach C, Koh JL, Flower DR, Wong L, Brusic V. FIMM, a database of functional molecular immunology: update 2002. Nucleic Acids Res, 2002, 30:226–9.
75. Bhasin M, Singh H, Raghava G. PS. (2002) MHCBN: A Comprehensive Database of MHC Binding and Non-Binding Peptides. Nucleic Acids Research, (online).
76. Corbet S, Nielsen HV, Vinner L, Lauem?ller SL, Therrien D, Tang S, Kronborg G, Mathiesen L, Chaplin P, Brunak S, Buus S, and Fomsgaard A. Optimisation and immune recognition of multiple novel conserved HLAA2,HIV-1-specific CTL epitopes. J Gen Virol. 2003, 84(Pt 9):2409-21.
77. Reche PA, Zhang H, Glutting JP, Reinherz EL. EPIMHC: a curated database of MHC-binding peptides for customized computational vaccinology. Bioinformatics. 2005, 21(9):2140-1.
78. Parker KC, Bednarek MA, Coligan JE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol. 1994 152:163–75.
79. .Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999 50:213–9.
80. Schueler-Furman O, Altuvia Y, Sette A, Margalit H. Structure-based prediction of binding peptides toMHCclass I molecules: application to a broad range of MHC alleles. Protein Sci 2000 9:1838–46.
81. Jung G, Fleckenstein B, von der Mulbe F, Wessels J, Niethammer D, Wiesmuller KH. From combinatorial libraries to MHC ligand motifs, T-cell superagonists and antagonists. Biologicals, 2001, 29:179–81
82. Yu K, Petrovsky N, Schonbach C, Koh JY, Brusic V. Methods for prediction of peptide binding to MHC molecules: a comparative study. Mol Med. 2002 8:137–48
83. Holzhutter HG, Frommel C, Kloetzel PM. A theoretical approach towards the identification of cleavage-determining amino acid motifs of the 20S proteasome.J Mol Biol. 1999 286:1251–65.
84. Raddrizzani L, Hammer J. Epitope scanning using virtual matrix-basedalgorithms. Brief Bioinform. 2000 1:179–89.
85. Doytchinova IA, Flower DR. Physicochemical explanation of peptide binding to HLA-A*0201 major histocompatibility complex: a three-dimensional quantitative structure-activity relationship study. Proteins. 2002 48:505–18.
86. Buus S, Lauem?ller SL,Worning P,Kesmir C, Frimurer T, Corbet S, Fomsgaard A, Hilden J, Holm A, and Brunak S. Sensitive quantitative predictions of peptide-MHC binding by a “Query by Committee” artificial neural network approach. Accepted for publication in Tissue Antigens, 2003.
87. Kuttler C, Nussbaum AK, Dick TP, Rammensee HG, Schild H, Hadeler KP. An algorithm for the prediction of proteasomal cleavages. J Mol Biol, 2000, 298:417–29.
88. Nussbaum AK, Kuttler C, H6adeler KP, Rammensee HG, Schild H. PAProC: a prediction algorithm for proteasomal cleavages available on the WWW. Immunogenetics, 2001, 53:87–94
89. Holzhutter HG, Frommel C, Kloetzel PM. A theoretical approach towards the identification of cleavage-determining amino acid motifs of the 20 S proteasome. J Mol Biol. 1999 286:1251–65.
90. Altuvia Y, Margalit H. Sequence signals for generation of antigenic peptides by the proteasome: implications for proteasomal cleavage mechanism. J Mol Biol. 2000 295:879–90.
91. Hakenberg J, Nussbaum AK, Schild H, Rammensee HG, Kuttler C, Holzhütter HG, Kloetzel PM, Kaufmann SH, Mollenkopf HJ. MAPPP: MHC class I antigenic peptide processing prediction. Appl Bioinformatics, 2003, 2(3):155-8
92. Lefranc MP, Giudicelli V, Kaas Q, Duprat E, Jabado-Michaloud J, Scaviner D, Ginestoux C, Clément O, Chaume D, Lefranc G. IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res, 2005,33(Database issue):D593-7.
93. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974, 139(2):380-97.
94. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992, 176(6):1693-702.
95. Evans JT, Cravens P, Lipsky PE, Garcia JV. Differentiation and expansion of lentivirus vector-marked dendritic cells derived from human CD34(+) cells. Hum Gene Ther, 2000, 11(18):2483-92.
96. Babatz J, Rollig C, Oelschlagel U, Zhao S, Ehninger G, Schmitz M, Bornhauser M. Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study. J Hematother Stem Cell Res. 2003 Oct;12(5):515-23
97. Zhu HF, Qiu WH, Lei P, Zhou W, Wen X, He FR, Li L, Dai H, Shen GX, Gong FL.IL-10 gene modified dendritic cells inhibit T helper type 1-mediated alloimmune responses and promote immunological tolerance in diabetes.Cell Mol Immunol. 2008 Feb;5(1):41-6
98. Windhagen A, S?nmez D, Hornig-Do HT, Kalinowsky A, Schwinzer R. Altered CD45 isoform expression in C77G carriers influences cytokine responsiveness and adhesion properties of T cells. Clin Exp Immunol. 2007, 150(3):509-17
99. Zhao X, Sato A, Dela Cruz CS, Linehan M, Luegering A, Kucharzik T, Shirakawa AK, Marquez G, Farber JM, Williams I, Iwasaki A. CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells. J Immunol. 2003, 171(6):2797-803
100.Zivkovic V, Basic M, Gligorijevic J, Pavlovic V, Lazarevic V, Petrovic A. Follicular dendritic cell sarcoma in the lymph nodes of the neck. Bratisl LekListy. 2007;108(8):368-70
101.Cong Y, Konrad A, Iqbal N, Elson CO.Probiotics and immune regulation of inflammatory bowel diseases.Curr Drug Targets Inflamm Allergy. 2003 , 2(2):145-54.
102.Burton GF, Kupp LI, McNalley EC, Tew JG. Follicular dendritic cells and B cell chemotaxis. Eur J Immunol. 1995 Apr;25(4):1105-8
103.Sacchi A, Cappelli G, Cairo C, Martino A, Sanarico N, D'Offizi G, Pupillo LP, Chenal H, De Libero G, Colizzi V, Vendetti S. Differentiation of monocytes into CD1a- dendritic cells correlates with disease progression in HIV-infected patients. J Acquir Immune Defic Syndr. 2007, 46(5):519-28.
104.Prechtel AT, Steinkasserer A.CD83: an update on functions and prospects of the maturation marker of dendritic cells. Arch Dermatol Res. 2007, 299(2):59-69.
105.Barrow L, Brown RD, Murray A, Sze DM, Pope B, Gibson J, Hart D, Joshua D.CMRF44+ dendritic cells from peripheral blood stem cell harvests of patients with myeloma as potential cellular vectors for idiotype vaccination. Leuk Lymphoma, 2003 , 44(12):2117-22
106.Freeman JL, Vari F, Hart DN. CMRF-56 immunoselected blood dendritic cell. preparations activated with GM-CSF induce potent antimyeloma cytotoxic T-cell responses. J Immunother. 2007, 30(7):740-8.
107.Radford KJ, Turtle CJ, Kassianos AJ, Vuckovic S, Gardiner D, Khalil D, Taylor K, Wright S, Gill D, Hart DN.Immunoselection of functional CMRF-56+ blood dendritic cells from multiple myeloma patients for immunotherapy. J Immunother, 2005 , 28(4):322-31.
108.Evans JT, Cravens P, Lipsky PE, Garcia JV..Differentiation and expansion of lentivirus vector-marked dendritic cells derived from human CD34(+) cells. Hum Gene Ther. 2000 Dec 10;11(18):2483-92.
109.Dohnal AM, Graffi S, Witt V, Eichstill C, Wagner D, Ul-Haq S, Wimmer D, Felzmann T. comparative ebaluation fo techniques for the manufacturing oftechniques for the manufacturing of dendritic cell-based-cancer vaccines. J Cell Mol Med. 2008 [Epub ahead of print]
110.Katsuaki Sato, Hitomi Nagayama, and Tsuneo A. Takahashi1. Generation of Dendritic Cells from Fresh and Frozen Cord Blood CD341 Cells. CRYOBIOLOGY, 1998, 37: 362–371 ()
111.Sch?kel K, Mayer E, Federle C, Schmitz M, Riethmüller G, Rieber EP. A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes. Eur J Immunol. 1998 Dec;28(12):4084-93.
112.Passetto Falc?o R, Pinto Sim?es B, Garcia AB, Fonseca BA, Terra Filho J.Aggressive variant of morphologically typical T large granular lymphocyte leukemia/lymphoma lacking NK cell markers. Acta Haematol, 2000;104(2-3):110-4
113.Peter Kelleher and Stella C. Knight. IL-12 increases CD80 expression and the stimulatory capacity of bone marrow-derived dendritic cells. International Immunology, 1998, 10( 6):749–755
114.Vremec D, Shortman K.Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol. 1997 Jul 15;159(2):565-73.
115.de Heusch M, Oldenhove G, Urbain J, Thielemans K, Maliszewski C, Leo O, Moser M.Depending on their maturation state, splenic dendritic cells induce the differentiation of CD4(+) T lymphocytes into memory and/or effector cells in vivo. Eur J Immunol. 2004, 34(7):1861-9.
116.Appelbaum FR, Sale GE, Storb R, Charrier K, Deeg HJ, Graham T, Wulff JC. Phenotyping of canine lymphoma with monoclonal antibodies directed at cell surface antigens: classification, morphology, clinical presentation and response to chemotherapy. Hematol Oncol. 1984, 2(2):151-68
117..Minghui zhang, Hua Tang,Zhenghong Guo,et al.splenic stroma drivesmature dendritic cells to differentiate into regulatory dendritic cells.Nature immunology. 2004.5(11):1124-1133.
118.Kitamura K, Takeda K, Koya T, Miyahara N, Kodama T, Dakhama A, Takai T, Hirano A, Tanimoto M, Harada M, Gelfand EW.Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation. J Immunol. 2007, 178(1):480-8.
119.Liu Y, Gao X, Masuda E, Redecha PB, Blank MC, Pricop L. Regulated expression of FcgammaR in human dendritic cells controls cross-presentation of antigen-antibody complexes. J Immunol. 2006 , 177(12):8440-7.
120.Morelli A, Larregina A, Chuluyán I, Kolkowski E, Fainboim L. Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells. Immunology. 1996, 89(1):126-34.
121.Robert Keller. Dendritic cells: their significance in health and disease. Immunology Letters, 2001, 78 (4) : 113-122.
122.Jacobs B, Wuttke M, Papewalis C, Seissler J, Schott M. Dendritic cell subtypes and in vitro generation of dendritic cells. Horm Metab Res. 2008 Feb;40(2):99-107.
123.Joanna Ashton-Chess, Gilles Blancho T. An in vitro evaluation of the potential suitability of peripheral blood CD14+ and bone marrow CD34+-derived dendritic cells for a tolerance inducing regimen in the primate B. Journal of Immunological Methods, 2005, 297:237-252
124.Ashton-Chess J, Blancho G.An in vitro evaluation of the potential suitability of peripheral blood CD14(+) and bone marrow CD34(+)-derived dendritic cells for a tolerance inducing regimen in the primate. J Immunol Methods. 2005 , 297(1-2):237-52.
125.Ivan Roitt, Jonathan Brostoff, David Male. Antigen presentation.Immunology, 2001, 6 (6):105-115.
126.Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O'Garra A Dendritic cells produce IL-12 and direct the development of Th1 cells from naǐve CD4 + cells. J Immunol, 1995, 154 (10) :5071-5079.
127.Stagg AJ, Hart AL, Knight SC, et al. The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria.Gut, 2003, 52 (10):1522-1529.
128.Salmon P, Arrighi JF, Piguet V, et al. Transduction of CD34 + cellswith lentiviral vectors enables the p roduction of large quantities of transgene expressing immature and mature dendritic cells [ J ]. J Gene med, 2001, 3 (4) : 311-320.
129.Merrick A, Errington F, Milward K, O'Donnell D, Harrington K, Bateman A, Pandha H, Vile R, Morrison E, Selby P, Melcher A.Immunosuppressive effects of radiation on human dendritic cells: reduced IL-12 production on activation and impairment of naive T-cell priming. Br J Cancer. 2005 Apr 25;92(8):1450-8.
130.陈蔚峰, 医学免疫学第四版. 北京:人民卫生出版社,2003.
131.Burgdorf S, Sch?lz C, Kautz A, Tampé R, Kurts C. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol. 2008 [Epub ahead of print]
132.. 金伯泉,.细胞与分子免疫学第二版. 北京: 科学出版社,2002.
133.McKenzie EJ, Taylor PR, Stillion RJ, Lucas AD, Harris J, Gordon S, Martinez-Pomares L. Mannose receptor expression and function define a new population of murine dendritic cells. J Immunol. 2007 Apr 15;178(8):4975-83.
134.Watts C, Matthews SP, Mazzeo D, Manoury B, Moss CX. Asparaginyl endopeptidase: case history of a class II MHC compartment protease. Immunol Rev. 2005, 207:218-28.
135.Lin ML, Zhan Y, Villadangos JA, Lew AM. The cell biology of cross-presentation and the role of dendritic cell subsets. Immunol Cell Biol. 2008 Feb 12; [Epub ahead of print]
136.Plitas G, Burt BM, Stableford JA, Nguyen HM, Welles AP, DeMatteo RP. Dendritic cells are required for effective cross-presentation in the murine liver. Hepatology. 2008 Apr;47(4):1343-51.
137.Di Pucchio T, Chatterjee B, Smed-S?rensen A, Clayton S, Palazzo A, Montes M, Xue Y, Mellman I, Banchereau J, Connolly JE. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 2008 Mar 30; [Epub ahead of print]
138.Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cells engaged in phagocytosis. Reis e Sousa C, Germain RN. J Exp Med. 1995, 182(3):841-51.
139.Huang H, Wang H, Wu ZQ, You CX, Luo RC, Yong L, Hermonat PL. Effects of two different antigen-loading methods on the activity of dendritic cell vaccine for colorectal carcinoma cell inhibition in vitro. Nan Fang Yi Ke Da Xue Xue Bao. 2007, 27(4):492-5.
140.Hegde VL, Singh NP, Nagarkatti PS, Nagarkatti M. CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation. J Leukoc Biol. 2008 Apr 3; [Epub ahead of print]
141.Gianotti L, Sargenti M, Galbiati F, Nespoli L, Brivio F, Rescigno M, Nespoli A. Phenotype and function of dendritic cells and T-lymphocyte polarization in the human colonic mucosa and adenocarcinoma. Eur J Surg Oncol. 2008 Mar 4; [Epub ahead of print]
142.Stimulation of cloned human T lymphocytes via the CD3 or CD28 molecules induces enhancement in vascular endothelial permeability to macromolecules with participation of type-1 and type-2 intercellularadhesion pathways. Eur J Immunol. 1990 Sep;20(9):1995-2003.
143.Poznansky MC, Olszak IT, Foxall R, Evans RH, Luster AD, Scadden DT. Active movement of T cells away from a chemokine. Nat Med. 2000 May;6(5):543-8
144.Grewal IS, Foellmer HG, Grewal KD, Xu J, Hardardottir F, Baron JL, Janeway CA Jr, Flavell RA. Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. Science. 1996 Sep 27;273(5283):1864-7.
145.Kikuchi T. Novel immunotherapeutic approach. Gan To Kagaku Ryoho. 2005, 32(4):453-7.
146.Brocker T.Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J Exp Med. 1997 , 186(8):1223-32
147.Liotta F, Frosali F, Querci V, Mantei A, Filì L, Maggi L, Mazzinghi B, Angeli R, Ronconi E, Santarlasci V, Biagioli T, Lasagni L, Ballerini C, Parronchi P, Scheffold A, Cosmi L, Maggi E, Romagnani S, Annunziato F. Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction. J Allergy Clin Immunol. 2008, 121(4):1000-5
148.Schwartz M, Yoles E.Macrophages and dendritic cells treatment of spinal cord injury: from the bench to the clinic. Acta Neurochir Suppl. 2005, 93:147-50.
149.Schlichting CL, Schareck WD, Nickel T, Weis M.Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation. Curr Med Chem. 2005, 12(16):1921-30.
150.150Beernink PT, Granoff DM. Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H Binding Protein Vaccines. Infect Immun. 2008, [Epub ahead of print]
151.Lowrie DB. DNA vaccination during TB treatment generates super-protective immunity. Gene Ther. 2005, 12(7):557-8.
152.Wing-Hong Kwan, Anna-Marija Helt, Concepción Mara?ón, Jean-Baptiste Barbaroux, Anne Hosmalin, Eva Harris, Wolf H. Fridman, and Chris G. F. Mueller. Dendritic Cell Precursors Are Permissive to Dengue Virus and Human Immunodeficiency Virus Infection Journal of Virology, 2005, 79(12):7291-7299
153.Cao H, Verg V, Martinache C, Leon A, Gorin NC, Bernard J, Lopez .MCryopreservation of Dendritic Cells Grown in Vitro from Monocytes for Their Future Clinical Use. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2000, 8(4):245-250
154.Kovarova L, Buchler T, Pour L, Zahradova L, Ocadlikova D, Svobodnik A, Penka M, Vorlicek J, Hajek R. Dendritic cell counts and their subsets during treatment of multiple myeloma. Neoplasma. 2007;54(4):297-303.
155.hang MJ, Huang J. Recent research progress of anti-tumor mechnism matrine. Zhongguo Zhong Yao Za Zhi. 2004, 29(2):115-8.
156.Morse MA, Lyerly HK.Dendritic cell-based approaches to cancer immunotherapy. Expert Opin Investig Drugs. 1998. 7(10):1617-27.
157.Kokowski K, Harnack U, Dorn DC, Pecher G. Quantification of the CD8(+) T cell response against a mucin epitope in patients with breast cancer. Arch Immunol Ther Exp (Warsz). 2008[Epub ahead of print]
158.Oelke M, Krueger C, Schneck JP. Technological advances in adoptive immunotherapy. Drugs Today (Barc). 2005, 41(1):13-21.
159.潘崚,郭晓楠,董作仁.白细胞介素 12 与肿瘤免疫河北医科大学学报1999,20(6):382-384
160.Nestle FO, Farkas A, Conrad C. Dendritic-cell-based therapeutic vaccination against cancer. Curr Opin Immunol. 2005, 17(2):163-9.
161.Alban Gervais, Jean Levêque, Fran?oise Bouet-Toussaint, Florence Burtin, Thierry Lesimple, Laurent Sulpice, Jean-Jacques Patard, Noelle Genetet,and Véronique Catros-Quemener. Breast Cancer Res. Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency. 2005, 7(3): 326-35..
162.Mahnke K, Qian Y, Fondel S, Brueck J, Becker C, Enk AH. Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res. 2005, 65(15):7007-12.
163.Akasaki Y, Black KL, Yu JS.Dendritic cell-based immunotherapy for malignant gliomas. Expert Rev Neurother, 2005, 5(4):497-508.
164.Lee WC, Wang HC, Hung CF, Huang PF, Lia CR, Chen MF.Vaccination of advanced hepatocellular carcinoma patients with tumor lysate-pulsed dendritic cells: a clinical trial. J Immunother, 2005, ;28(5):496-504.
165.Tripathi P, Agrawal S.Immunobiology of human imunodeficiency virus infection. Indian J Med Microbiol. 2007, 25(4):311-22.
166.Wei lu, Luiz Claudio Arraes, Wylla Tatiana Ferreira , Jean-Marie Andrieu . Therapeutic dendritic-cell vaccine for chronic HIV-I infection. Nature Medcine 2004, 10:1350-65.
167.Wei Lu, Xiaoxian Wu, Yaozeng Lu, Weizhong Guo, Jean-Marie Andrieu . Therapeutic dendritic-cell vaccine for simian AIDS.NATURE MEDICINE. 2003, 9(1): 27-32
168.Jana Babatz Christoph Ro¨ llig Ba¨ rbel Lo¨ bel Gunnar Folprecht Michael Haack Heinrich Gu¨ nther Claus-Henning Ko¨ hne Gerhard Ehninger Marc Schmitz Martin Bornha¨ user. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination altered peptide ligand-loaded dendritic cells. Cancer Immunol Immunother.2005.
169.Anorlu RI.What is the significance of the HPV epidemic? Can J Urol. 2008 Feb;15(1):3860-5.
170.Watson-Jones D, Weiss HA, Rusizoka M, et al. Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania.
171.Garnett GP.Role of herd immunity in determining the effect of vaccines against sexually transmitted disease.J Infect Dis. 2005 Feb 1;191 Suppl 1:S97-106.
172.González C, Canals J, Ortiz M, Mu?oz L, Torres M, García-Saiz A, Del Amo J.Prevalence and determinants of high-risk human papillomavirus (HPV) infection and cervical cytological abnormalities in imprisoned women.Epidemiol Infect. 2008 Feb;136(2):215-21.
173.Suprynowicz FA, Disbrow GL, Krawczyk E, Simic V, Lantzky K, Schlegel R. HPV-16 E5 oncoprotein upregulates lipid raft components caveolin-1 and ganglioside GM1 at the plasma membrane of cervical cells. Oncogene, 2008, 27(8):1071-8.
174.Cameron JE, Hagensee ME. Human papillomavirus infection and disease in the HIV+ individual. Cancer Treat Res. 2007; 133:185-213.
175.Eisemann J, Mühl-Zürbes P, Steinkasserer A, Kummer M.Infection of mature dendritic cells with herpes simplex virus type 1 interferes with the interferon signaling pathway. Immunobiology. 2007;212(9-10):877-86.
176.杨朝晖, 钱起丰, 吴志华. 尖锐湿疣患者自然杀伤细胞活性及其与血清白介素-12 关系的研究. 广东医学院学报, 2000, 18(3): 233-234
177.Thomas KJ, Smith KL, Youde SJ, Evans M, Fiander AN, Borysiewicz LK, Man S.HPV16 E6(29-38)-specific T cells kill cervical carcinoma cells despite partial evasion of T-cell effector function. Int J Cancer. 2008,122(12):2791-2799 [Epub ahead of print]
178.黄伟峰,郝飞,刁庆春,钟白玉. HPV16 E7 多肽冲击的树突状细胞治疗尖锐湿疣的 I 临床初步观察.第三大学学报. 2004, 26(15):1388-90
179.王少扬; 林玉梅; 马卫闽; 戚少然; 兰凤华 IL -12 对慢性乙型肝炎患者TH1 和 TH2 分化的影响.免疫学杂志. 2001; 17(6): 466-468
180.Ruo-Bing Li, Hong-Song Chen, Yao Xie, Ran Fei, Xu Cong, Dong Jiang, Song-Xia Wang, Lai Wei, Yu Wang. Dendritic cells from chronic hepatitis B patients can induce HBV antigen-specific T cell responses.World JGastroenterol 2004, 10(11):1578-1582
181.杜清友,刘明旭,王福生,雷周云,孙文兵,陈菊梅,吴祖泽. CIK 细胞体内外抗肝癌细胞作用.中国癌症杂志, 2001, 11(4):325-330
182.Maini MK, et al. The role of virus-specific CD8+ cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med, 2000, 9:1269
183.Guidottl LG, et al. Virus clearance without destruction of infected cells during acute HBV infection. Science. 1999; 284:825
184.TangRx,Cao FG, et al. Detection DNA and its existence status in liver tissues and peripheral blood lymphocytes from chronic hepatitis B patients. World J Gastroenterol. 1999; 5:359-36l
185.吴玉章. CTL 的免疫识别和效应机制.中国免疫学杂志, 2000, 17:171-175
186.徐薇,熊思东 .细胞因子介导的 CTL 非杀伤性途径. 国外医学.微生物学分册, 2001,24:6
187.成军,李莉.清除乙型肝炎病毒的非细胞裂解机制.世界华人消化杂志. 2002; 10(1):73-76.
188.Salazar-Mather TP, Lewis CA, Biron CA. Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1 alpha delivery to the liver. J Clin Invest. 2002, 110:321-330
189.Webster GJ, Reignet S, Maini MK, Whalley SA, Ogg GS, King A, Brown D, Amlot PL, Williams R, Vergani D, Dusheiko GM, Bertoletti A.. Incubation phase of acute hepatitis B in man:dynamic of cellular immune mechanism. Hepatology 2000;32:1117-1124
190.Soheila Tavakoli, Wibke Schwerin, Andreas Rohwer, Sina Hoffmann, Sandra Weyer,1 Robert Weth, Helga Meise, Helmut Diepolder,Michael Geissler, Peter R. Galle, Hanns F. Lo¨hrL and Wulf O. Bo¨ cher.Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection. Journal of General Virology (2004), 85, 2829–2836
191.Guidotti LG, Rochford R,Chung J, Shapiro M, Purcell R, Chisari FV. Viralclearance without destruction of infected cells during acute HBV infection. Science, 1999, 284(5415):825-9
192.Kakimi K, Guidotti LG, Koezuka Y, Chisari FV.. Nature killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med, 2000, 192:921-930
193.Tamaru M, Nishioji K, Kobayashi Y, Watanabe Y, Itoh Y, Okanoue T, Murai M, Matsushima K, Narumi S.. Liver-infiltrating T lymphocytes are attracted selectively by IFN-induced protein-10. Cytokine 2000, 12:299-308
194.Kakimi K, Lane TE, Wieland S, Asensio VC, Campbell IL, Chisari FV, Guidotti LG.. Blocking chemokine responsive to gamma-2/interferon(IFN)-gamma inducible protein and monokine induced by IFN-gamma activitiy in vivo reduces the pathogenetic but not the antiviral of hepatitis B virus-specific cytotoxic T lymphocytes. J Exp Med, 2001, 194:1755-1766
195.Boni C, Penna A, Ogg GS, Bertoletti A, Pilli M, Cavallo C, Cavalli A, Urbani S, Boehme R, Panebianco R, Fiaccadori F, Ferrari C. Lamivudine treatment can overcome cytotoxic T cell hyporesponsiveness in chronic hepatitis B:new perspectives for immune therapy. Hepatology, 2001, 33:963-971
196.Sk Md Fazle Akbar, Norio Horiike, Morikazu Onji. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection. World J Gastroenterol, 2006, 12(18): 2876-2883.
197.Akbar SM, Furukawa S, Hasebe A, Horiike N, Michitaka K, Onji M. Production and efficacy of a dendritic cell-based therapeutic vaccine for murine chronic hepatitis B virus carrierer. Int J Mol Med, 2004, 14(2):295-9.
198.I YG, Chen M, Zhang DZ, Wang ZY, Zeng WQ, Shi XF, Guo Y, Guo SH, Ren H. Clinical research on the treatment effect of autologous dendritic cell vaccine on the patients with chronic hepatitis B. Zhonghua Gan Zang BingZa Zhi. 2003 , 11(4):206-8.
199.Huang B, Mao CP, Peng S, He L, Hung CF, Wu TC.Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency. Vaccine, 2007, 25(45):7824-31.
200.Cranmer LD, Trevor KT, Hersh EM. Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother, 2004, 53(4):275-306.
201.Therapeutic effect of autologous dendritic cell vaccine on patients with chronic hepatitis B: A clinical study. World J Gastroenterol 2005, 11(12):1806-1808
202.Qiao-Ling Sun, Wei Ran. Review of cytokine profiles in patients with hepatitisWorld J Gastroenterol, 2004, 10(12):1709-1715
203.Victor Appay , Sarah L. Rowland-Jones. The assessment of antigen-specific CD8+ T cells through the combination of MHC class I tetramer and intracellular staining. Journal of Immunological Methods, 2002 ,268:9 – 19
204.Dikici B, Kalayci AG, Ozgenc F, Bosnak M, Davutoglu M, Ece A, Ozkan T, Ozeke T, Yagci RV, Haspolat K. Therapeutic vaccination in the immunotolerant phase of children with chronic hepatitis B infection. Pediatr Infect Dis J. 2003, 22(4):345-9.
205.Dikici B, Bosnak M, Ucmak H, Dagli A, Ece A, Haspolat K. Failure of therapeutic vaccination using hepatitis B surface antigen vaccine in the immunotolerant phase of children with chronic hepatitis B infection. J Gastroenterol Hepatol. 2003, 18(2):218-22.
206.袁正宏,方昕,郑玲洁,姚忻,何丽芳,闻玉梅.免疫途径及载体对乙肝病毒DNA 疫苗免疫效果影响的研究.中华微生物和免疫学杂志, 1999, 19(1):25-28
207.Jones LA, Salgaller ML.Therapeutic potential of dendritic-based vaccines. Expert Opin Investig Drugs, 1999, 8(7):1007-16.
208.Dauer M, Schad K, Herten J, Junkmann J, Bauer C, Kiefl R, Endres S, Eigler A.FastDC derived from human monocytes within 48 h effectively prime tumor antigen-specific cytotoxic T cells. J Immunol Methods. 2005, 302(1-2):145-55.
209.傅晋翔,刘艳,梁建英.脐血 CD34+细胞体外扩增及树突状.细胞诱导的实验研究.实用肿瘤杂志, 2001, l6(4):231-234。
210.Papamichail M, Gutierrez C, Holborow EJ. The use of nlon fibre as a method of separation human lymphocyte subpopulations. J Immunol Methods, 1976, 11:225-229.
211.Morimoto C, Reinherz EL, Borel Y, Schlossman SF. Direct demonstration of the human suppressor induced subset by antr T cell antibodies. J Immunol, 1983, 130(1):157-61.
212.Yu K, Petrovsky N, Schonbach C, Koh JY, Brusic V.Methods for prediction of peptide binding to MHC molecules: a comparative study. Mol Med. 2002, 8(3):137-48.
213.Huang H, Bi XG, Yuan JY, Xu SL, Guo XL, Xiang J. Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy. Gene Ther, 2005, 12(12):999-1010
214.Rener M; Claesson M H; Bregenholt S; Ropke M. An improved method for the detection of peptide-induced upregulation of HIA-A*0201 molecules on TAP-deficient T2 cells. Exp.Clin. Immunogenet. 1996, 13, 30-35.
215.Hata T, Hoshi T, Kanamori K, Matsumae A, Sano Y, Shima T, Sugawara R. Mitomycin a new antibiotic from Streptomyces. J Antibiot (Tokyor), 1956, 9 (4):141-146.
216.Anne Hosmalin, Muriel Andrieu, Estelle Loing, Jean-Francois Desoutter, Daniel Hanau, He′le`ne Gras-Masse, Alice Dautry-Varsat, Jean-Ge′rard Guillet. Lipopeptide presentation pathway in dendritic cells. Immunology Letters 2001.79:97–100
217.Anca Reschner, AntoniaMoretta, Regine Landmann, Michael Heberer,Giulio C.Spagnoli and Elisabetta Padovan. The ester-bonded palmitoyl side chains of Pam3CysSerLys4 lipopeptide account for its powerful adjuvanticity to HLA class I-restricted CD8+ T lymphocytes。Eur. J. Immunol, 2003, 33: 2044–2052
218.韦嘉, 姚集鲁. 细胞因子网络与病毒性肝炎. 国外医学内科学分册, 1999, 26 (12 ):511-517.
219.Maltoni M, Fabbri L , Nanni O Scarpi E, Pezzi L, Flamini E, Riccobon A, Derni S, Pallotti G, Amadori D. Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients.Support Care Cancer, 1997, 5(2) :130-135.
220.Chang HR, Bistrian B. The role of cytokines in the catabolic consequences of infection and injury. JPEN J Parenter Enteral Nutr, 1998; 22(3) :156-166
221.Andrassy RJ, Chwals WJ. Nutritional support of the pediatric oncology patient. Nutrition. 1998;14(1):124-129
222.张卓然.细胞培养学与细胞培养技术.上海科学技术出版社, 2004. 456-7
223.刘艳荣,陈珊珊,于弘. 流式细胞术计数 CD34 阳性细胞的标准化与质量控制. 中国实验血液学杂志, 2000, 8(4):302-306
224.魏然, 夏作理, 陈彬, 韩纪举, 任道凌, 杨明峰. 慢性乙肝患者外周血CD14+单核细胞的功能状态. 世界华人消化杂, 2004, 12(3):618-621
225.Trinchieri G, Gerosa F. Immunoregulation by interleukin-12. J Leukoc Biol. 1996, 59(4):505-11.
226.Lebel-Binay S, Berger A, Zinzindohoué F, Cugnenc P, Thiounn N, Fridman WH, Pagès F. Interleukin-18: biological properties and clinical implications. Eur Cytokine Netw, 2000, 11(1):15-26
227.Shows TB, Sakaguchi AY, Naylor SL.Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease. Adv Hum Genet, 1982, 12:341-452.
228.Gajewski, T.F, and Fitch, F.W. Anti-proliferative effects of IFN- gamma in murine regulation. J.Immunol, 1988, 140:4245.-52
2. Chentoufi AA, Zhang X, Lamberth K, Dasgupta G, Bettahi I, Nguyen A, Wu M, Zhu X, Mohebbi A, Buus S, Wechsler SL, Nesburn AB, Benmohamed L. HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D. J Immunol, 2008, 180(1):426-37
3. Sidney J, Assarsson E, Moore C, Ngo S, Pinilla C, Sette A, Peters B. Quantitative peptide binding motifs for 19 human and mouse MHC class I molecules derived using positional scanning combinatorial peptide libraries. Immunome Res, 2008, 25(4):2
4. Mirano-Bascos D, Tary-Lehmann M, Landry SJ. Antigen structure influences helper T-cell epitope dominance in the human immune response to HIV envelope glycoprotein gp120. Eur J Immunol. 2008[Epub ahead of print]
5. Wilson CC, Newman MJ, Livingston BD, Mawhinney S, Forster JE, Scott J, Schooley RT, Benson CA. Clinical Phase 1 Safety and Immunogenicity Testing of an Epitope-based DNA Vaccine in HIV-1-infected Subjects Receiving Highly Active Antiretroviral Therapy (HAART). Clin Vaccine Immunol, 2008[Epub ahead of print]
6. Jarchum I, Nichol L, Trucco M, Santamaria P, Dilorenzo TP. Identification of novel IGRP epitopes targeted in type 1 diabetes patients. Clin Immunol, 2008 ,19[Epub ahead of print]
7. Han N, J?rvinen KM, Cocco RR, Busse PJ, Sampson HA, Beyer K. Identification of amino acids critical for IgE-binding to sequential epitopes of bovine kappa-casein and the similarity of these epitopes to the corresponding human kappa-casein sequence.
8. Wilkinson RA, Evans JR, Jacobs JM, Slunaker D, Pincus SH, Pinter A, Parkos CA, Burritt JB, Teintze M. Peptides selected from a phage display library with an HIV-neutralizing antibody elicit antibodies to HIV gp120 in rabbits, but not to the same epitope. AIDS Res Hum Retroviruses. 2007, 23(11):1416-279
9. Fagerberg T, Cerottini JC, Michielin O. Structural prediction of peptides bound to MHC class I.J Mol Biol, 2006 , 356(2):521-46
10. Nishikawa M, Takemoto S, Takakura Y. Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm, 2008, 1354(1-2):23-7.
11. Okochi M, Hayashi H, Ito A, Kato R, Tamura Y, Sato N, Honda H. Identification of HLA-A24-restricted epitopes with high affinities to Hsp70 using peptide arrays. J Biosci Bioeng, 2008, 105(3):198-203
12. Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol, 2008, 9(1):8
13. Ge Q, Holler PD, Mahajan VS, Nuygen T, Eisen HN, Chen J. Development of CD4+ T cells expressing a nominally MHC class I-restricted T cell receptor by two different mechanisms. Proc Natl Acad Sci U S A, 2006, 103(6):1822-7.
14. Mishto M, Luciani F, Holzhütter HG, Bellavista E, Santoro A, Textoris-Taube K, Franceschi C, Kloetzel PM, Zaikin A. Modeling the in vitro 20S proteasome activity: the effect of PA28-alphabeta and of the sequence and length of polypeptides on the degradation kinetics. J Mol Biol, 2008, 377(5):1607-17
15. Marcilla M, Villasevil EM, de Castro JA.Tripeptidyl peptidase II is dispensable for the generation of both proteasome-dependent andproteasome-independent ligands of HLA-B27 and other class I molecules. Eur J Immunol, 2008, 38(3):631-9
16. Hwang MS, Kim KN, Lee JH, Park YI. Identification of amino acid sequences determining interaction between the cucumber mosaic virus-encoded 2a polymerase and 3a movement proteins. J Gen Virol, 2007, 88(Pt12):3445-51
17. Saudemont A, Hamrouni A, Marchetti P, Liu J, Jouy N, Hetuin D, Colucci F, Quesnel B. Dormant tumor cells develop cross-resistance to apoptosis induced by CTLs or imatinib mesylate via methylation of suppressor of cytokine signaling 1. Cancer Res, 2007, 67(9):4491-8
18. 支 轶,吴玉章,万瑛. 生物信息学方法在 CTL 表位预测中的应用. 免疫学杂志, 2005, 21(2):155-150
19. 林治华,吴玉章. 计算机辅助 T 细胞表位鉴定. 生命的化学, 2004, 24(5):397-399
20. Zajac P, Oertli D, Spagnoli GC, Noppen C, Schaefer C, Heberer M, Marti WR. Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in vitro stimulation with a replication-incompetent vaccinia virus encoding MART-1/Melan-A 27-35 epitope. Int J Cancer, 1997, 71(3):491-6
21. Sahin U,Tureci O, Pfreundschuh M. Serological identification of human tumor antifens. Curr Opin Immunol, 1997;9:709-16
22. 张立红, 张晓楠, 曲萍, 叶菁, 隋延仿, 郭爱林. 突变的肝细胞生长因子受体被肝癌细胞 HLA-A2 分子递呈的实验研究。中华医学杂志, 2001;81:30-32
23. 郭爱林,张敏,隋延仿. 一个新的 MAGE-1 抗原肽为肝癌细胞表面HLA-B7 分子递呈. 中国免疫学杂志,2001;5(17):527-530
24. Stevanovic S. Identification of tumou-associated T-cell epitopes for vaccine development. Nature Rev, 2002,2:1-7
25. Lucas S, De Smet C, Arden KC, Viars CS, Lethé B, Lurquin C, Boon T. Identification of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res. 1998, 58(4):743-52.
26. Chen L. Mimotopes of cytolytic T lymphocytes in cancer immunotherapy. Curr Opin Immunol, 1999, 11:219-222
27. Tsurui H, Takahashi T. Prediction of T-cell epitope. J Pharmacol Sci, 2007, 105(4):299-316
28. Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol, 2008, 9(1):8
29. Malcherek G, Falk K, R?tzschke O, Rammensee HG, Stevanovi? S, Gnau V, Jung G, Melms A. Natural peptide ligand motifs of two HLA molecules associated with myasthenia gravis. Int Immunol. 1993, 5(10):1229-37
30. Keles S, van der Laan MJ, Vulpe C. Regulatory motif finding by logic regression. Bioinformatics, 2004, 20(16):2799-811
31. Kast WM, Brandt RM, Sidney J, Drijfhout JW, Kubo RT, Grey HM, Melief CJ, Sette A.Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. J Immunol, 1994, 152(8):3904-12
32. Kubo RT, Sette A, Grey HM, Appella E, Sakaguchi K, Zhu NZ, Arnott D, Sherman N, Shabanowitz J, Michel H.Definition of specific peptide motifs for four major HLA—A alleles.J lmmunol 1994,152(9):3913·3925
33. Ruppert J, Sidney J, Celis E, Kubo RT, Grey HM, Sette A.Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929-37
34. Keles S, van der Laan MJ, Vulpe C. Regulatory motif finding by logic regression. Bioinformatics. 2004, 20(16):2799-811
35. 黄健.HLA 超型与表位肽超基序及其理论与现实意义.国外医学免疫学分册 2001,24(6):305-306
36. Altfeld MA, Livingston B,Reshamwala N,et a1.Identification of novel HLA-A2-restricted human immunedeficiency virus type 1-specific cytotoxic T—lymphocyte epitopes predicted by the HLA-A2 supertype peptide-bindingmotif.J Virol, 2001, 75(3):1301-1311
37. Endo D, Kanaho Y, Park MK.Gen Comp Endocrinol. Expression of sex steroid hormone-related genes in the embryo of the leopard gecko. 2008, 155(1):70-8
38. Davenport MP, Ho Shon IA, Hill AV. An empirical method for the prediction of T-cell epitopes. Immunogenetics. 1995, 42(5):392-7
39. Dick TP, Stevanovi? S, Keilholz W, Ruppert T, Koszinowski U, Schild H, Rammensee HG. The making of the dominant MHC class I ligand SYFPEITHI.
40. Gomez-Nunez M, Pinilla-Ibarz J, Dao T, May RJ, Pao M, Jaggi JS, Scheinberg DA. Peptide binding motif predictive algorithms correspond with experimental binding of leukemia vaccine candidate peptides to HLA-A*0201 molecules. Leuk Res. 2006, 30(10):1293-8
41. ParkerKC,Bednarek MA,ColiganJE.Schemefor ranking poten—tim HLA—A2 binding peptides based on independent binding of in—dividual peptide side-chains.J lmmunol, 1994,152(1):l63-175
42. Stryhn A, Pedersen LO, Romme T, Holm CB, Holm A, Buus S. Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding. Eur J Immunol, 1996, 26(8):1911-8.
43. Gulukota K,Sidney J,Sette A。et a1.Two complementary methods for predicting poptides binding major histcompatibilIIy complex molecules. J Mol Biol, 1997, 267(5):1258-1267
44. Dick TP, Stevanovi? S, Keilholz W, Ruppert T, Koszinowski U, Schild H, Rammensee HG. The making of the dominant MHC class I ligandSYFPEITHI. Eur J Immunol. 1998 Aug;28(8):2478-86
45. Reche PA, Glutting JP, Zhang H, Reinherz EL. Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics. 2004 Sep;56(6):405-19
46. Singh H,Raghava GP.Propred I:Prediction of promiscuous MHC class—I binding sites.Bioinformaties, 2003,19(8):l009-l014
47. Marusarz RK, Sayeh MR. Neural network-based multimode fiber-optic information transmission. Appl Opt. 2001, 40(2):219-27.
48. Adams HP, Kodol JA.Prediction of binding to MHC dass I molecules.J Immunol Methods 1995,185(2) 181—190.
49. Bohr H , et al. Protein secondary structure and homology by neural network. FEBS Lett , 1988 , 241 : 171 – 176
50. Wikmington. Use neural network for problem solving. Chem Eng Prog , 1993, 89 (4): 44 – 50
51. Gulukota K, Sidney J, Sette A, DeLisi C. Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J Mol Biol. 1997; 267(5):1258-67
52. Brusie V,Petrovsky N,Zhang G,et a1.Prediction of promiscuous peptides that bind HLA class I molecules.Immunol Cel Biol, 2002, 80(3):280-285.
53. Schonbach C,Kun Y,Brusie V.L 丑 rge—scale COmputational iden·tifieation of HIV T—cell epitopes.Immunol Cell Biol 2002,80(3):300-306.
54. 李孝安, 张晓缋. 神经网络与神经计算导论. 西安: 西北工业大学出版社, 1994. 34 – 36
55. Altuvia Y, Schueler O, Margalit H.Ranking potential binding peptides to MHC molecules by a computational threading approach. J Mol Biol, 1995, 249(2):244-50.
56. Doytchinova IA, Walshe V, Borrow P, Flower DR. Towards thechemometric dissection of peptide--HLA-A*0201 binding affinity: comparison of local and global QSAR models. J Comput Aided Mol Des. 2005, 19(3):203-12
57. Chiang RA, Meng EC, Huang CC, Ferrin TE, Babbitt PC.The Structure Superposition Database. Nucleic Acids Res, 2003, 31(1):505-10.
58. Scherf T, Hiller R, Naider F, Levitt M, Anglister J. Induced peptide conformations in different antibody complexes: molecular modeling of the three-dimensional structure of peptide-antibody complexes using NMR-derived distance restraints. Biochemistry, 1992, 31(30):6884-97
59. Lim JS,Kim S,Lee HG,et a1.Selection ofpeptides that bind to the HLA-A2 . 1 molecule by molecular modeling. Mol Immunol 1996, 33(2):221-230.
60. Altuvia Y,Sehueler 0,Margalit H.Ranking potential binding poptides to MHC molecules by a computational threading approach. J Mol Biol 1995, 249(2):244-250.
61. Altuvia Y,Sette A,Sidney J,et a1.A structure-based algorithm to predict potential binding peptides to MHC molecules with hydrophobie binding pockets. Hum lmmunol, 1997, 58(1):1 一 l1.
62. Sehueler Furman O,Elber R, Margalit H. Knowledge-based structure prediction of MHC class l bound peptides:a study of 23 complexes.Fold Des, 1998, 3(6):549-564.
63. Schueler-Furman O, Altuvia Y, Sette A, Margalit H. Structure based prediction of binding peptides to MHC class I molecules:application to a broad range of MHC allele.Protein Sci, 2000, 9(9):1838—1846
64. Zhang C,Andemon A,Delisi.Structural principles that govern the poptide—binding motifs of class I MHC molecules.J Mol Bid, 1998, 281(5):929-947.
65. Logean A,Rognan D.Recovery of known T-cell epitopes by computational scanning of a viral ganome.J Comput Aided Mol Des, 2002,16(4):229-243
66. Holzhutter HG,Frommel C,Kloetzel PM.A theoretical approach towards the identification of cleavage-determining amino acid motifs ofthe 20 S proteasome.J Mol Biol,1999,286(4):1251—1265.
67. Nussbaum AK, Kuttler C, Hadeler KP, Rammensee HG, Schild H. Nussbaum AK,Kuttler C,Hadeler KP,el a1.PAProC:a prediction algorithm for proteasomal cleavages available on the www.Immunogenetics,2001,53(2):87-94
68. Kesmir C,Nnssbaum AK,Sctnld H.el a1.Prediction of proteasome cleavage motifs by neural networks.Protein Eng,2002,15(4):287-296
69. Duniel S,Brusic V,Caillat.Zucman S.Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules.J Immunol,1998,161(2):617-624.
70. Doytchinova IA,Flower DR.Physicochemical explanation of peptide binding to HLA-A*0201 major histocompatibility complex: a three-dimensional quantitative structure-activity relationship study.Proteins,2002,48 (3):505—518.
71. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovi? S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999 Nov;50(3-4):213-9.
72. Brusic V, Rudy G, Harrison LC. MHCPEP, a database of MHC-binding peptides update 1997. Nucleic Acids Res, 1998, 26:368–71
73. Blythe MJ, Doytchinova IA, Flower DR. JenPep: a database of quantitative functional peptide data for immunology. Bioinformatics. 2002 18:434–9.
74. Schonbach C, Koh JL, Flower DR, Wong L, Brusic V. FIMM, a database of functional molecular immunology: update 2002. Nucleic Acids Res, 2002, 30:226–9.
75. Bhasin M, Singh H, Raghava G. PS. (2002) MHCBN: A Comprehensive Database of MHC Binding and Non-Binding Peptides. Nucleic Acids Research, (online).
76. Corbet S, Nielsen HV, Vinner L, Lauem?ller SL, Therrien D, Tang S, Kronborg G, Mathiesen L, Chaplin P, Brunak S, Buus S, and Fomsgaard A. Optimisation and immune recognition of multiple novel conserved HLAA2,HIV-1-specific CTL epitopes. J Gen Virol. 2003, 84(Pt 9):2409-21.
77. Reche PA, Zhang H, Glutting JP, Reinherz EL. EPIMHC: a curated database of MHC-binding peptides for customized computational vaccinology. Bioinformatics. 2005, 21(9):2140-1.
78. Parker KC, Bednarek MA, Coligan JE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol. 1994 152:163–75.
79. .Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999 50:213–9.
80. Schueler-Furman O, Altuvia Y, Sette A, Margalit H. Structure-based prediction of binding peptides toMHCclass I molecules: application to a broad range of MHC alleles. Protein Sci 2000 9:1838–46.
81. Jung G, Fleckenstein B, von der Mulbe F, Wessels J, Niethammer D, Wiesmuller KH. From combinatorial libraries to MHC ligand motifs, T-cell superagonists and antagonists. Biologicals, 2001, 29:179–81
82. Yu K, Petrovsky N, Schonbach C, Koh JY, Brusic V. Methods for prediction of peptide binding to MHC molecules: a comparative study. Mol Med. 2002 8:137–48
83. Holzhutter HG, Frommel C, Kloetzel PM. A theoretical approach towards the identification of cleavage-determining amino acid motifs of the 20S proteasome.J Mol Biol. 1999 286:1251–65.
84. Raddrizzani L, Hammer J. Epitope scanning using virtual matrix-basedalgorithms. Brief Bioinform. 2000 1:179–89.
85. Doytchinova IA, Flower DR. Physicochemical explanation of peptide binding to HLA-A*0201 major histocompatibility complex: a three-dimensional quantitative structure-activity relationship study. Proteins. 2002 48:505–18.
86. Buus S, Lauem?ller SL,Worning P,Kesmir C, Frimurer T, Corbet S, Fomsgaard A, Hilden J, Holm A, and Brunak S. Sensitive quantitative predictions of peptide-MHC binding by a “Query by Committee” artificial neural network approach. Accepted for publication in Tissue Antigens, 2003.
87. Kuttler C, Nussbaum AK, Dick TP, Rammensee HG, Schild H, Hadeler KP. An algorithm for the prediction of proteasomal cleavages. J Mol Biol, 2000, 298:417–29.
88. Nussbaum AK, Kuttler C, H6adeler KP, Rammensee HG, Schild H. PAProC: a prediction algorithm for proteasomal cleavages available on the WWW. Immunogenetics, 2001, 53:87–94
89. Holzhutter HG, Frommel C, Kloetzel PM. A theoretical approach towards the identification of cleavage-determining amino acid motifs of the 20 S proteasome. J Mol Biol. 1999 286:1251–65.
90. Altuvia Y, Margalit H. Sequence signals for generation of antigenic peptides by the proteasome: implications for proteasomal cleavage mechanism. J Mol Biol. 2000 295:879–90.
91. Hakenberg J, Nussbaum AK, Schild H, Rammensee HG, Kuttler C, Holzhütter HG, Kloetzel PM, Kaufmann SH, Mollenkopf HJ. MAPPP: MHC class I antigenic peptide processing prediction. Appl Bioinformatics, 2003, 2(3):155-8
92. Lefranc MP, Giudicelli V, Kaas Q, Duprat E, Jabado-Michaloud J, Scaviner D, Ginestoux C, Clément O, Chaume D, Lefranc G. IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res, 2005,33(Database issue):D593-7.
93. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974, 139(2):380-97.
94. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992, 176(6):1693-702.
95. Evans JT, Cravens P, Lipsky PE, Garcia JV. Differentiation and expansion of lentivirus vector-marked dendritic cells derived from human CD34(+) cells. Hum Gene Ther, 2000, 11(18):2483-92.
96. Babatz J, Rollig C, Oelschlagel U, Zhao S, Ehninger G, Schmitz M, Bornhauser M. Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study. J Hematother Stem Cell Res. 2003 Oct;12(5):515-23
97. Zhu HF, Qiu WH, Lei P, Zhou W, Wen X, He FR, Li L, Dai H, Shen GX, Gong FL.IL-10 gene modified dendritic cells inhibit T helper type 1-mediated alloimmune responses and promote immunological tolerance in diabetes.Cell Mol Immunol. 2008 Feb;5(1):41-6
98. Windhagen A, S?nmez D, Hornig-Do HT, Kalinowsky A, Schwinzer R. Altered CD45 isoform expression in C77G carriers influences cytokine responsiveness and adhesion properties of T cells. Clin Exp Immunol. 2007, 150(3):509-17
99. Zhao X, Sato A, Dela Cruz CS, Linehan M, Luegering A, Kucharzik T, Shirakawa AK, Marquez G, Farber JM, Williams I, Iwasaki A. CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells. J Immunol. 2003, 171(6):2797-803
100.Zivkovic V, Basic M, Gligorijevic J, Pavlovic V, Lazarevic V, Petrovic A. Follicular dendritic cell sarcoma in the lymph nodes of the neck. Bratisl LekListy. 2007;108(8):368-70
101.Cong Y, Konrad A, Iqbal N, Elson CO.Probiotics and immune regulation of inflammatory bowel diseases.Curr Drug Targets Inflamm Allergy. 2003 , 2(2):145-54.
102.Burton GF, Kupp LI, McNalley EC, Tew JG. Follicular dendritic cells and B cell chemotaxis. Eur J Immunol. 1995 Apr;25(4):1105-8
103.Sacchi A, Cappelli G, Cairo C, Martino A, Sanarico N, D'Offizi G, Pupillo LP, Chenal H, De Libero G, Colizzi V, Vendetti S. Differentiation of monocytes into CD1a- dendritic cells correlates with disease progression in HIV-infected patients. J Acquir Immune Defic Syndr. 2007, 46(5):519-28.
104.Prechtel AT, Steinkasserer A.CD83: an update on functions and prospects of the maturation marker of dendritic cells. Arch Dermatol Res. 2007, 299(2):59-69.
105.Barrow L, Brown RD, Murray A, Sze DM, Pope B, Gibson J, Hart D, Joshua D.CMRF44+ dendritic cells from peripheral blood stem cell harvests of patients with myeloma as potential cellular vectors for idiotype vaccination. Leuk Lymphoma, 2003 , 44(12):2117-22
106.Freeman JL, Vari F, Hart DN. CMRF-56 immunoselected blood dendritic cell. preparations activated with GM-CSF induce potent antimyeloma cytotoxic T-cell responses. J Immunother. 2007, 30(7):740-8.
107.Radford KJ, Turtle CJ, Kassianos AJ, Vuckovic S, Gardiner D, Khalil D, Taylor K, Wright S, Gill D, Hart DN.Immunoselection of functional CMRF-56+ blood dendritic cells from multiple myeloma patients for immunotherapy. J Immunother, 2005 , 28(4):322-31.
108.Evans JT, Cravens P, Lipsky PE, Garcia JV..Differentiation and expansion of lentivirus vector-marked dendritic cells derived from human CD34(+) cells. Hum Gene Ther. 2000 Dec 10;11(18):2483-92.
109.Dohnal AM, Graffi S, Witt V, Eichstill C, Wagner D, Ul-Haq S, Wimmer D, Felzmann T. comparative ebaluation fo techniques for the manufacturing oftechniques for the manufacturing of dendritic cell-based-cancer vaccines. J Cell Mol Med. 2008 [Epub ahead of print]
110.Katsuaki Sato, Hitomi Nagayama, and Tsuneo A. Takahashi1. Generation of Dendritic Cells from Fresh and Frozen Cord Blood CD341 Cells. CRYOBIOLOGY, 1998, 37: 362–371 ()
111.Sch?kel K, Mayer E, Federle C, Schmitz M, Riethmüller G, Rieber EP. A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes. Eur J Immunol. 1998 Dec;28(12):4084-93.
112.Passetto Falc?o R, Pinto Sim?es B, Garcia AB, Fonseca BA, Terra Filho J.Aggressive variant of morphologically typical T large granular lymphocyte leukemia/lymphoma lacking NK cell markers. Acta Haematol, 2000;104(2-3):110-4
113.Peter Kelleher and Stella C. Knight. IL-12 increases CD80 expression and the stimulatory capacity of bone marrow-derived dendritic cells. International Immunology, 1998, 10( 6):749–755
114.Vremec D, Shortman K.Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol. 1997 Jul 15;159(2):565-73.
115.de Heusch M, Oldenhove G, Urbain J, Thielemans K, Maliszewski C, Leo O, Moser M.Depending on their maturation state, splenic dendritic cells induce the differentiation of CD4(+) T lymphocytes into memory and/or effector cells in vivo. Eur J Immunol. 2004, 34(7):1861-9.
116.Appelbaum FR, Sale GE, Storb R, Charrier K, Deeg HJ, Graham T, Wulff JC. Phenotyping of canine lymphoma with monoclonal antibodies directed at cell surface antigens: classification, morphology, clinical presentation and response to chemotherapy. Hematol Oncol. 1984, 2(2):151-68
117..Minghui zhang, Hua Tang,Zhenghong Guo,et al.splenic stroma drivesmature dendritic cells to differentiate into regulatory dendritic cells.Nature immunology. 2004.5(11):1124-1133.
118.Kitamura K, Takeda K, Koya T, Miyahara N, Kodama T, Dakhama A, Takai T, Hirano A, Tanimoto M, Harada M, Gelfand EW.Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation. J Immunol. 2007, 178(1):480-8.
119.Liu Y, Gao X, Masuda E, Redecha PB, Blank MC, Pricop L. Regulated expression of FcgammaR in human dendritic cells controls cross-presentation of antigen-antibody complexes. J Immunol. 2006 , 177(12):8440-7.
120.Morelli A, Larregina A, Chuluyán I, Kolkowski E, Fainboim L. Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells. Immunology. 1996, 89(1):126-34.
121.Robert Keller. Dendritic cells: their significance in health and disease. Immunology Letters, 2001, 78 (4) : 113-122.
122.Jacobs B, Wuttke M, Papewalis C, Seissler J, Schott M. Dendritic cell subtypes and in vitro generation of dendritic cells. Horm Metab Res. 2008 Feb;40(2):99-107.
123.Joanna Ashton-Chess, Gilles Blancho T. An in vitro evaluation of the potential suitability of peripheral blood CD14+ and bone marrow CD34+-derived dendritic cells for a tolerance inducing regimen in the primate B. Journal of Immunological Methods, 2005, 297:237-252
124.Ashton-Chess J, Blancho G.An in vitro evaluation of the potential suitability of peripheral blood CD14(+) and bone marrow CD34(+)-derived dendritic cells for a tolerance inducing regimen in the primate. J Immunol Methods. 2005 , 297(1-2):237-52.
125.Ivan Roitt, Jonathan Brostoff, David Male. Antigen presentation.Immunology, 2001, 6 (6):105-115.
126.Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O'Garra A Dendritic cells produce IL-12 and direct the development of Th1 cells from naǐve CD4 + cells. J Immunol, 1995, 154 (10) :5071-5079.
127.Stagg AJ, Hart AL, Knight SC, et al. The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria.Gut, 2003, 52 (10):1522-1529.
128.Salmon P, Arrighi JF, Piguet V, et al. Transduction of CD34 + cellswith lentiviral vectors enables the p roduction of large quantities of transgene expressing immature and mature dendritic cells [ J ]. J Gene med, 2001, 3 (4) : 311-320.
129.Merrick A, Errington F, Milward K, O'Donnell D, Harrington K, Bateman A, Pandha H, Vile R, Morrison E, Selby P, Melcher A.Immunosuppressive effects of radiation on human dendritic cells: reduced IL-12 production on activation and impairment of naive T-cell priming. Br J Cancer. 2005 Apr 25;92(8):1450-8.
130.陈蔚峰, 医学免疫学第四版. 北京:人民卫生出版社,2003.
131.Burgdorf S, Sch?lz C, Kautz A, Tampé R, Kurts C. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol. 2008 [Epub ahead of print]
132.. 金伯泉,.细胞与分子免疫学第二版. 北京: 科学出版社,2002.
133.McKenzie EJ, Taylor PR, Stillion RJ, Lucas AD, Harris J, Gordon S, Martinez-Pomares L. Mannose receptor expression and function define a new population of murine dendritic cells. J Immunol. 2007 Apr 15;178(8):4975-83.
134.Watts C, Matthews SP, Mazzeo D, Manoury B, Moss CX. Asparaginyl endopeptidase: case history of a class II MHC compartment protease. Immunol Rev. 2005, 207:218-28.
135.Lin ML, Zhan Y, Villadangos JA, Lew AM. The cell biology of cross-presentation and the role of dendritic cell subsets. Immunol Cell Biol. 2008 Feb 12; [Epub ahead of print]
136.Plitas G, Burt BM, Stableford JA, Nguyen HM, Welles AP, DeMatteo RP. Dendritic cells are required for effective cross-presentation in the murine liver. Hepatology. 2008 Apr;47(4):1343-51.
137.Di Pucchio T, Chatterjee B, Smed-S?rensen A, Clayton S, Palazzo A, Montes M, Xue Y, Mellman I, Banchereau J, Connolly JE. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 2008 Mar 30; [Epub ahead of print]
138.Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cells engaged in phagocytosis. Reis e Sousa C, Germain RN. J Exp Med. 1995, 182(3):841-51.
139.Huang H, Wang H, Wu ZQ, You CX, Luo RC, Yong L, Hermonat PL. Effects of two different antigen-loading methods on the activity of dendritic cell vaccine for colorectal carcinoma cell inhibition in vitro. Nan Fang Yi Ke Da Xue Xue Bao. 2007, 27(4):492-5.
140.Hegde VL, Singh NP, Nagarkatti PS, Nagarkatti M. CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation. J Leukoc Biol. 2008 Apr 3; [Epub ahead of print]
141.Gianotti L, Sargenti M, Galbiati F, Nespoli L, Brivio F, Rescigno M, Nespoli A. Phenotype and function of dendritic cells and T-lymphocyte polarization in the human colonic mucosa and adenocarcinoma. Eur J Surg Oncol. 2008 Mar 4; [Epub ahead of print]
142.Stimulation of cloned human T lymphocytes via the CD3 or CD28 molecules induces enhancement in vascular endothelial permeability to macromolecules with participation of type-1 and type-2 intercellularadhesion pathways. Eur J Immunol. 1990 Sep;20(9):1995-2003.
143.Poznansky MC, Olszak IT, Foxall R, Evans RH, Luster AD, Scadden DT. Active movement of T cells away from a chemokine. Nat Med. 2000 May;6(5):543-8
144.Grewal IS, Foellmer HG, Grewal KD, Xu J, Hardardottir F, Baron JL, Janeway CA Jr, Flavell RA. Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. Science. 1996 Sep 27;273(5283):1864-7.
145.Kikuchi T. Novel immunotherapeutic approach. Gan To Kagaku Ryoho. 2005, 32(4):453-7.
146.Brocker T.Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J Exp Med. 1997 , 186(8):1223-32
147.Liotta F, Frosali F, Querci V, Mantei A, Filì L, Maggi L, Mazzinghi B, Angeli R, Ronconi E, Santarlasci V, Biagioli T, Lasagni L, Ballerini C, Parronchi P, Scheffold A, Cosmi L, Maggi E, Romagnani S, Annunziato F. Human immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction. J Allergy Clin Immunol. 2008, 121(4):1000-5
148.Schwartz M, Yoles E.Macrophages and dendritic cells treatment of spinal cord injury: from the bench to the clinic. Acta Neurochir Suppl. 2005, 93:147-50.
149.Schlichting CL, Schareck WD, Nickel T, Weis M.Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation. Curr Med Chem. 2005, 12(16):1921-30.
150.150Beernink PT, Granoff DM. Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H Binding Protein Vaccines. Infect Immun. 2008, [Epub ahead of print]
151.Lowrie DB. DNA vaccination during TB treatment generates super-protective immunity. Gene Ther. 2005, 12(7):557-8.
152.Wing-Hong Kwan, Anna-Marija Helt, Concepción Mara?ón, Jean-Baptiste Barbaroux, Anne Hosmalin, Eva Harris, Wolf H. Fridman, and Chris G. F. Mueller. Dendritic Cell Precursors Are Permissive to Dengue Virus and Human Immunodeficiency Virus Infection Journal of Virology, 2005, 79(12):7291-7299
153.Cao H, Verg V, Martinache C, Leon A, Gorin NC, Bernard J, Lopez .MCryopreservation of Dendritic Cells Grown in Vitro from Monocytes for Their Future Clinical Use. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2000, 8(4):245-250
154.Kovarova L, Buchler T, Pour L, Zahradova L, Ocadlikova D, Svobodnik A, Penka M, Vorlicek J, Hajek R. Dendritic cell counts and their subsets during treatment of multiple myeloma. Neoplasma. 2007;54(4):297-303.
155.hang MJ, Huang J. Recent research progress of anti-tumor mechnism matrine. Zhongguo Zhong Yao Za Zhi. 2004, 29(2):115-8.
156.Morse MA, Lyerly HK.Dendritic cell-based approaches to cancer immunotherapy. Expert Opin Investig Drugs. 1998. 7(10):1617-27.
157.Kokowski K, Harnack U, Dorn DC, Pecher G. Quantification of the CD8(+) T cell response against a mucin epitope in patients with breast cancer. Arch Immunol Ther Exp (Warsz). 2008[Epub ahead of print]
158.Oelke M, Krueger C, Schneck JP. Technological advances in adoptive immunotherapy. Drugs Today (Barc). 2005, 41(1):13-21.
159.潘崚,郭晓楠,董作仁.白细胞介素 12 与肿瘤免疫河北医科大学学报1999,20(6):382-384
160.Nestle FO, Farkas A, Conrad C. Dendritic-cell-based therapeutic vaccination against cancer. Curr Opin Immunol. 2005, 17(2):163-9.
161.Alban Gervais, Jean Levêque, Fran?oise Bouet-Toussaint, Florence Burtin, Thierry Lesimple, Laurent Sulpice, Jean-Jacques Patard, Noelle Genetet,and Véronique Catros-Quemener. Breast Cancer Res. Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency. 2005, 7(3): 326-35..
162.Mahnke K, Qian Y, Fondel S, Brueck J, Becker C, Enk AH. Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. Cancer Res. 2005, 65(15):7007-12.
163.Akasaki Y, Black KL, Yu JS.Dendritic cell-based immunotherapy for malignant gliomas. Expert Rev Neurother, 2005, 5(4):497-508.
164.Lee WC, Wang HC, Hung CF, Huang PF, Lia CR, Chen MF.Vaccination of advanced hepatocellular carcinoma patients with tumor lysate-pulsed dendritic cells: a clinical trial. J Immunother, 2005, ;28(5):496-504.
165.Tripathi P, Agrawal S.Immunobiology of human imunodeficiency virus infection. Indian J Med Microbiol. 2007, 25(4):311-22.
166.Wei lu, Luiz Claudio Arraes, Wylla Tatiana Ferreira , Jean-Marie Andrieu . Therapeutic dendritic-cell vaccine for chronic HIV-I infection. Nature Medcine 2004, 10:1350-65.
167.Wei Lu, Xiaoxian Wu, Yaozeng Lu, Weizhong Guo, Jean-Marie Andrieu . Therapeutic dendritic-cell vaccine for simian AIDS.NATURE MEDICINE. 2003, 9(1): 27-32
168.Jana Babatz Christoph Ro¨ llig Ba¨ rbel Lo¨ bel Gunnar Folprecht Michael Haack Heinrich Gu¨ nther Claus-Henning Ko¨ hne Gerhard Ehninger Marc Schmitz Martin Bornha¨ user. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination altered peptide ligand-loaded dendritic cells. Cancer Immunol Immunother.2005.
169.Anorlu RI.What is the significance of the HPV epidemic? Can J Urol. 2008 Feb;15(1):3860-5.
170.Watson-Jones D, Weiss HA, Rusizoka M, et al. Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania.
171.Garnett GP.Role of herd immunity in determining the effect of vaccines against sexually transmitted disease.J Infect Dis. 2005 Feb 1;191 Suppl 1:S97-106.
172.González C, Canals J, Ortiz M, Mu?oz L, Torres M, García-Saiz A, Del Amo J.Prevalence and determinants of high-risk human papillomavirus (HPV) infection and cervical cytological abnormalities in imprisoned women.Epidemiol Infect. 2008 Feb;136(2):215-21.
173.Suprynowicz FA, Disbrow GL, Krawczyk E, Simic V, Lantzky K, Schlegel R. HPV-16 E5 oncoprotein upregulates lipid raft components caveolin-1 and ganglioside GM1 at the plasma membrane of cervical cells. Oncogene, 2008, 27(8):1071-8.
174.Cameron JE, Hagensee ME. Human papillomavirus infection and disease in the HIV+ individual. Cancer Treat Res. 2007; 133:185-213.
175.Eisemann J, Mühl-Zürbes P, Steinkasserer A, Kummer M.Infection of mature dendritic cells with herpes simplex virus type 1 interferes with the interferon signaling pathway. Immunobiology. 2007;212(9-10):877-86.
176.杨朝晖, 钱起丰, 吴志华. 尖锐湿疣患者自然杀伤细胞活性及其与血清白介素-12 关系的研究. 广东医学院学报, 2000, 18(3): 233-234
177.Thomas KJ, Smith KL, Youde SJ, Evans M, Fiander AN, Borysiewicz LK, Man S.HPV16 E6(29-38)-specific T cells kill cervical carcinoma cells despite partial evasion of T-cell effector function. Int J Cancer. 2008,122(12):2791-2799 [Epub ahead of print]
178.黄伟峰,郝飞,刁庆春,钟白玉. HPV16 E7 多肽冲击的树突状细胞治疗尖锐湿疣的 I 临床初步观察.第三大学学报. 2004, 26(15):1388-90
179.王少扬; 林玉梅; 马卫闽; 戚少然; 兰凤华 IL -12 对慢性乙型肝炎患者TH1 和 TH2 分化的影响.免疫学杂志. 2001; 17(6): 466-468
180.Ruo-Bing Li, Hong-Song Chen, Yao Xie, Ran Fei, Xu Cong, Dong Jiang, Song-Xia Wang, Lai Wei, Yu Wang. Dendritic cells from chronic hepatitis B patients can induce HBV antigen-specific T cell responses.World JGastroenterol 2004, 10(11):1578-1582
181.杜清友,刘明旭,王福生,雷周云,孙文兵,陈菊梅,吴祖泽. CIK 细胞体内外抗肝癌细胞作用.中国癌症杂志, 2001, 11(4):325-330
182.Maini MK, et al. The role of virus-specific CD8+ cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med, 2000, 9:1269
183.Guidottl LG, et al. Virus clearance without destruction of infected cells during acute HBV infection. Science. 1999; 284:825
184.TangRx,Cao FG, et al. Detection DNA and its existence status in liver tissues and peripheral blood lymphocytes from chronic hepatitis B patients. World J Gastroenterol. 1999; 5:359-36l
185.吴玉章. CTL 的免疫识别和效应机制.中国免疫学杂志, 2000, 17:171-175
186.徐薇,熊思东 .细胞因子介导的 CTL 非杀伤性途径. 国外医学.微生物学分册, 2001,24:6
187.成军,李莉.清除乙型肝炎病毒的非细胞裂解机制.世界华人消化杂志. 2002; 10(1):73-76.
188.Salazar-Mather TP, Lewis CA, Biron CA. Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1 alpha delivery to the liver. J Clin Invest. 2002, 110:321-330
189.Webster GJ, Reignet S, Maini MK, Whalley SA, Ogg GS, King A, Brown D, Amlot PL, Williams R, Vergani D, Dusheiko GM, Bertoletti A.. Incubation phase of acute hepatitis B in man:dynamic of cellular immune mechanism. Hepatology 2000;32:1117-1124
190.Soheila Tavakoli, Wibke Schwerin, Andreas Rohwer, Sina Hoffmann, Sandra Weyer,1 Robert Weth, Helga Meise, Helmut Diepolder,Michael Geissler, Peter R. Galle, Hanns F. Lo¨hrL and Wulf O. Bo¨ cher.Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infection. Journal of General Virology (2004), 85, 2829–2836
191.Guidotti LG, Rochford R,Chung J, Shapiro M, Purcell R, Chisari FV. Viralclearance without destruction of infected cells during acute HBV infection. Science, 1999, 284(5415):825-9
192.Kakimi K, Guidotti LG, Koezuka Y, Chisari FV.. Nature killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med, 2000, 192:921-930
193.Tamaru M, Nishioji K, Kobayashi Y, Watanabe Y, Itoh Y, Okanoue T, Murai M, Matsushima K, Narumi S.. Liver-infiltrating T lymphocytes are attracted selectively by IFN-induced protein-10. Cytokine 2000, 12:299-308
194.Kakimi K, Lane TE, Wieland S, Asensio VC, Campbell IL, Chisari FV, Guidotti LG.. Blocking chemokine responsive to gamma-2/interferon(IFN)-gamma inducible protein and monokine induced by IFN-gamma activitiy in vivo reduces the pathogenetic but not the antiviral of hepatitis B virus-specific cytotoxic T lymphocytes. J Exp Med, 2001, 194:1755-1766
195.Boni C, Penna A, Ogg GS, Bertoletti A, Pilli M, Cavallo C, Cavalli A, Urbani S, Boehme R, Panebianco R, Fiaccadori F, Ferrari C. Lamivudine treatment can overcome cytotoxic T cell hyporesponsiveness in chronic hepatitis B:new perspectives for immune therapy. Hepatology, 2001, 33:963-971
196.Sk Md Fazle Akbar, Norio Horiike, Morikazu Onji. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection. World J Gastroenterol, 2006, 12(18): 2876-2883.
197.Akbar SM, Furukawa S, Hasebe A, Horiike N, Michitaka K, Onji M. Production and efficacy of a dendritic cell-based therapeutic vaccine for murine chronic hepatitis B virus carrierer. Int J Mol Med, 2004, 14(2):295-9.
198.I YG, Chen M, Zhang DZ, Wang ZY, Zeng WQ, Shi XF, Guo Y, Guo SH, Ren H. Clinical research on the treatment effect of autologous dendritic cell vaccine on the patients with chronic hepatitis B. Zhonghua Gan Zang BingZa Zhi. 2003 , 11(4):206-8.
199.Huang B, Mao CP, Peng S, He L, Hung CF, Wu TC.Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency. Vaccine, 2007, 25(45):7824-31.
200.Cranmer LD, Trevor KT, Hersh EM. Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother, 2004, 53(4):275-306.
201.Therapeutic effect of autologous dendritic cell vaccine on patients with chronic hepatitis B: A clinical study. World J Gastroenterol 2005, 11(12):1806-1808
202.Qiao-Ling Sun, Wei Ran. Review of cytokine profiles in patients with hepatitisWorld J Gastroenterol, 2004, 10(12):1709-1715
203.Victor Appay , Sarah L. Rowland-Jones. The assessment of antigen-specific CD8+ T cells through the combination of MHC class I tetramer and intracellular staining. Journal of Immunological Methods, 2002 ,268:9 – 19
204.Dikici B, Kalayci AG, Ozgenc F, Bosnak M, Davutoglu M, Ece A, Ozkan T, Ozeke T, Yagci RV, Haspolat K. Therapeutic vaccination in the immunotolerant phase of children with chronic hepatitis B infection. Pediatr Infect Dis J. 2003, 22(4):345-9.
205.Dikici B, Bosnak M, Ucmak H, Dagli A, Ece A, Haspolat K. Failure of therapeutic vaccination using hepatitis B surface antigen vaccine in the immunotolerant phase of children with chronic hepatitis B infection. J Gastroenterol Hepatol. 2003, 18(2):218-22.
206.袁正宏,方昕,郑玲洁,姚忻,何丽芳,闻玉梅.免疫途径及载体对乙肝病毒DNA 疫苗免疫效果影响的研究.中华微生物和免疫学杂志, 1999, 19(1):25-28
207.Jones LA, Salgaller ML.Therapeutic potential of dendritic-based vaccines. Expert Opin Investig Drugs, 1999, 8(7):1007-16.
208.Dauer M, Schad K, Herten J, Junkmann J, Bauer C, Kiefl R, Endres S, Eigler A.FastDC derived from human monocytes within 48 h effectively prime tumor antigen-specific cytotoxic T cells. J Immunol Methods. 2005, 302(1-2):145-55.
209.傅晋翔,刘艳,梁建英.脐血 CD34+细胞体外扩增及树突状.细胞诱导的实验研究.实用肿瘤杂志, 2001, l6(4):231-234。
210.Papamichail M, Gutierrez C, Holborow EJ. The use of nlon fibre as a method of separation human lymphocyte subpopulations. J Immunol Methods, 1976, 11:225-229.
211.Morimoto C, Reinherz EL, Borel Y, Schlossman SF. Direct demonstration of the human suppressor induced subset by antr T cell antibodies. J Immunol, 1983, 130(1):157-61.
212.Yu K, Petrovsky N, Schonbach C, Koh JY, Brusic V.Methods for prediction of peptide binding to MHC molecules: a comparative study. Mol Med. 2002, 8(3):137-48.
213.Huang H, Bi XG, Yuan JY, Xu SL, Guo XL, Xiang J. Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy. Gene Ther, 2005, 12(12):999-1010
214.Rener M; Claesson M H; Bregenholt S; Ropke M. An improved method for the detection of peptide-induced upregulation of HIA-A*0201 molecules on TAP-deficient T2 cells. Exp.Clin. Immunogenet. 1996, 13, 30-35.
215.Hata T, Hoshi T, Kanamori K, Matsumae A, Sano Y, Shima T, Sugawara R. Mitomycin a new antibiotic from Streptomyces. J Antibiot (Tokyor), 1956, 9 (4):141-146.
216.Anne Hosmalin, Muriel Andrieu, Estelle Loing, Jean-Francois Desoutter, Daniel Hanau, He′le`ne Gras-Masse, Alice Dautry-Varsat, Jean-Ge′rard Guillet. Lipopeptide presentation pathway in dendritic cells. Immunology Letters 2001.79:97–100
217.Anca Reschner, AntoniaMoretta, Regine Landmann, Michael Heberer,Giulio C.Spagnoli and Elisabetta Padovan. The ester-bonded palmitoyl side chains of Pam3CysSerLys4 lipopeptide account for its powerful adjuvanticity to HLA class I-restricted CD8+ T lymphocytes。Eur. J. Immunol, 2003, 33: 2044–2052
218.韦嘉, 姚集鲁. 细胞因子网络与病毒性肝炎. 国外医学内科学分册, 1999, 26 (12 ):511-517.
219.Maltoni M, Fabbri L , Nanni O Scarpi E, Pezzi L, Flamini E, Riccobon A, Derni S, Pallotti G, Amadori D. Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients.Support Care Cancer, 1997, 5(2) :130-135.
220.Chang HR, Bistrian B. The role of cytokines in the catabolic consequences of infection and injury. JPEN J Parenter Enteral Nutr, 1998; 22(3) :156-166
221.Andrassy RJ, Chwals WJ. Nutritional support of the pediatric oncology patient. Nutrition. 1998;14(1):124-129
222.张卓然.细胞培养学与细胞培养技术.上海科学技术出版社, 2004. 456-7
223.刘艳荣,陈珊珊,于弘. 流式细胞术计数 CD34 阳性细胞的标准化与质量控制. 中国实验血液学杂志, 2000, 8(4):302-306
224.魏然, 夏作理, 陈彬, 韩纪举, 任道凌, 杨明峰. 慢性乙肝患者外周血CD14+单核细胞的功能状态. 世界华人消化杂, 2004, 12(3):618-621
225.Trinchieri G, Gerosa F. Immunoregulation by interleukin-12. J Leukoc Biol. 1996, 59(4):505-11.
226.Lebel-Binay S, Berger A, Zinzindohoué F, Cugnenc P, Thiounn N, Fridman WH, Pagès F. Interleukin-18: biological properties and clinical implications. Eur Cytokine Netw, 2000, 11(1):15-26
227.Shows TB, Sakaguchi AY, Naylor SL.Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease. Adv Hum Genet, 1982, 12:341-452.
228.Gajewski, T.F, and Fitch, F.W. Anti-proliferative effects of IFN- gamma in murine regulation. J.Immunol, 1988, 140:4245.-52