TLR3在HBsAg阳性孕妇婴儿HBV宫内感染中作用机制的研究
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摘要
目的
①了解HBsAg阳性孕妇婴儿脐静脉血PBMC中TLR3与HBV宫内感染的关系。
②探讨HBsAg阳性孕妇婴儿脐静脉血PBMC中相关免疫细胞与HBV宫内感染的关系。
③探讨TLR3在HBsAg阳性孕妇婴儿HBV宫内感染中可能的作用机制。
方法
①收集2011年7月至2012年1月于太原市传染病医院妇产科分娩的HBsAg阳性孕妇产后脐血共52例。无菌采集分娩时脐血抗凝血30ml，并收集母儿的流行病学资料。
②婴儿脐静脉血PBMC的分离及培养，体外HBV干预宫内感染组和非宫内感染组，以HBV+PolyI:C干预宫内感染组婴儿PBMC。
③多色流式细胞术（FCM）对两组TLR3蛋白表达的荧光强度值以及T细胞、B细胞、DC细胞和CD4+CD25+Treg的百分比进行测定。
结果
①采用多色FCM测定TLR3蛋白表达荧光强度值，经比较：非宫内感染组的TLR3蛋白表达的平均荧光强度值（32.18±11.36）高于宫内感染组（30.29±11.04），差异无统计学意义（t=0.410,P=0.684）；宫内感染组TLR3活化后（即PolyI:C刺激后），TLR3蛋白表达的平均荧光强度值（32.16±9.40）升高，与非宫内感染组的（32.18±11.36）相比，无统计学差异（t=-1.824,P=0.078）。
②采用多色FCM测定B细胞的百分比，经比较：非宫内感染组的B细胞的百分比（7.38±6.40）高于宫内感染组（6.76±4.01），没有统计学差异（t=0.210,P=0.834）；宫内感染组TLR3活化后，B细胞的百分比（5.14±2.64）降低，与非宫内感染组（7.38±6.40）比较，差异没有统计学意义（t=0.768,P=0.447）。
③非宫内感染组的CD4+T细胞的百分比（41.14±20.08）高于宫内感染组（33.82±2.60），差异尚不能认为有统计学意义（t=0.618,P=0.543）；非宫内感染组的CD8+T细胞的百分比（11.30±5.87）与宫内感染组（11.14±9.64）相比，差异无统计学意义（t=0.041,P=0.968）；非宫内感染组的CD4+/CD8+比值（4.30±2.28）与宫内感染组的（4.75±3.23）比较，差异尚不能认为有统计学意义（t=-0.30,P=0.767）。
④非宫内感染组的mDC的百分比（0.84±0.58）高于宫内感染组（0.67±0.34），差异尚不能认为有统计学意义（t=-0.485,P=0.633）；非宫内感染组的pDC（0.92±0.91）与宫内感染组的（0.91±0.46）比较，差异没有统计学意义（t=0.020,P=0.984）。
⑤非宫内感染组的CD4~+CD25~+Treg细胞的百分比（4.69±3.41）与宫内感染组（3.00）比较，差异无统计学意义（t=0.474,P=0.646）。
结论
①非宫内感染组的TLR3蛋白表达平均荧光强度值高于宫内感染组，而宫内感染组经PolyI:C刺激后其表达水平升高，提示宫内感染可能与婴儿TLR3表达有关。
②非宫内感染组的B细胞、CD4~+T细胞、mDC的百分比高于宫内感染组，提示宫内感染与婴儿B细胞、CD4~+T细胞、mDC表达可能有关。
③本次研究未发现宫内感染与CD8~+T细胞、pDC、CD4~+CD25+Treg细胞的百分比以及CD4~+/CD8~+比值相关，有待于进一步研究。
OBJECTIVE:
①To investigate the relationship between TLR3 in the PBMC of the unbilicalvein blood of babies whose mothers are HBsAg posotive and HBV intrauterineinfection.
②To explore the relationship between immunocytes concerning PBMC and theHBV intrauterine infection.
③To explore the mechanism of TLR3 in HBV intrauterine infection .
METHODS:
①The epidemiological base line data and umbilical vein blood of 52HBsAg-positive pregnant women were collected from Taiyuan infectious hospitalfrom July 2011 to January 2012.
②Experiment was performed in vitro: The PBMC were separated from umbilicalvein blood and then were cultured. The PBMC of HBV intrauterine infection wereintervented by HBV+PolyI:C and HBV.The PBMC with negative HBV intrauterineinfection were intervented only by HBV.
③The protein expession of TLR3 and the percentages of B-cells,T-cells,DC andTreg were detected by FCM.
RESULTS:
①The expression level of TLR3 protein was higher in PBMC with negativeHBV intrauterine infection than that in PBMC with positive HBV intrauterineinfection(32.18±11.36,30.29±11.04),but no significant difference was observed（t=0.410，P=0.684）.After the intervention of PolyI:C, the expression level of TLR3increased,but still no significant difference was observed (32.18±11.36, 32.16±9.40;t=-1.824,P=0.078).
②Proportion of B-cells with negative HBV intrauterine uninfection was higherthan the ones with positive HBV intrauterine infection(7.38±6.40;6.76±4.01),but nosignificant difference was observed (t=0.210,P=0.834).After the intervention ofPolyI:C, percentage of B-cells with positive HBV intrauterine uninfection decreased,but still no significant difference was observed(7.38±6.40,5.14±2.64;t=0.768,P=0.447).
③Percentage of CD4+T-cells with negative HBV intrauterine infection washigher than the ones with positive HBV intrauterine infection,but no significantdifference was observed(41.14±20.08,33.82±2.60;t=0.618,P=0.543),while percentageof CD8+T-cells with negative HBV intrauterine infection was higher than the oneswith positive HBV intrauterine infection(11.30±5.87,11.14±9.64) with no significantdifference(11.30±5.87,11.14±9.64;t=0.041,P=0.968).The difference of ratio ofCD4+T-cells to CD8+T-cells between negative and positive HBV intrauterine infectiongroups was not significant(4.30±2.28,4.75±3.23;t=-0.30,P=0.767).
④Percentage of mDC with negaitive HBV intrauterine infection was higher thanthe one with positive HBV intrauterine infection(0.84±0.58,0.67±0.34) but with nosignificant difference (t=-0.485,P=0.633).While percentage of pDC with negaitiveHBV intrauterine infection was higher than the one with positive HBV intrauterineinfection,but with no significant difference there was(0.92±0.91,0.91±0.46;t=0.020,P=0.984).
⑤Percentage of CD4+CD25+Treg with negative HBV intrauterine infection washigher than the one with positive HBV intrauterine infection(4.69±3.41,3.00),but withno significant difference between them(t=0.474,P=0.646).
CONCLUSIONS:
①The fact that expression level of TLR3 protein with negative HBVintrauterine infection was higher than the one with HBV intrauterine infection andthat intervention of PolyI:C caused the increase of the expression level of TLR3protein indicates that HBV intrauterine infection may be linked to TLR3 proteinexpresson.
②The fact that the percentages of B-cells,CD4+T-cells and mDC with negativeHBV intrauterine infection were higher than the ones with positive intrauterineinfection indicates that the B-cells,CD4+T-cells,mDC may be a protective factoragainst placenta HBV infection.
③The fact that association between percentage of CD8+T-cells,pDC as well asCD4+CD25+Treg and the CD4+/CD8+T-cells was not discovered indicates that furtherstudy is required.
①了解HBsAg阳性孕妇婴儿脐静脉血PBMC中TLR3与HBV宫内感染的关系。
②探讨HBsAg阳性孕妇婴儿脐静脉血PBMC中相关免疫细胞与HBV宫内感染的关系。
③探讨TLR3在HBsAg阳性孕妇婴儿HBV宫内感染中可能的作用机制。
方法
①收集2011年7月至2012年1月于太原市传染病医院妇产科分娩的HBsAg阳性孕妇产后脐血共52例。无菌采集分娩时脐血抗凝血30ml，并收集母儿的流行病学资料。
②婴儿脐静脉血PBMC的分离及培养，体外HBV干预宫内感染组和非宫内感染组，以HBV+PolyI:C干预宫内感染组婴儿PBMC。
③多色流式细胞术（FCM）对两组TLR3蛋白表达的荧光强度值以及T细胞、B细胞、DC细胞和CD4+CD25+Treg的百分比进行测定。
结果
①采用多色FCM测定TLR3蛋白表达荧光强度值，经比较：非宫内感染组的TLR3蛋白表达的平均荧光强度值（32.18±11.36）高于宫内感染组（30.29±11.04），差异无统计学意义（t=0.410,P=0.684）；宫内感染组TLR3活化后（即PolyI:C刺激后），TLR3蛋白表达的平均荧光强度值（32.16±9.40）升高，与非宫内感染组的（32.18±11.36）相比，无统计学差异（t=-1.824,P=0.078）。
②采用多色FCM测定B细胞的百分比，经比较：非宫内感染组的B细胞的百分比（7.38±6.40）高于宫内感染组（6.76±4.01），没有统计学差异（t=0.210,P=0.834）；宫内感染组TLR3活化后，B细胞的百分比（5.14±2.64）降低，与非宫内感染组（7.38±6.40）比较，差异没有统计学意义（t=0.768,P=0.447）。
③非宫内感染组的CD4+T细胞的百分比（41.14±20.08）高于宫内感染组（33.82±2.60），差异尚不能认为有统计学意义（t=0.618,P=0.543）；非宫内感染组的CD8+T细胞的百分比（11.30±5.87）与宫内感染组（11.14±9.64）相比，差异无统计学意义（t=0.041,P=0.968）；非宫内感染组的CD4+/CD8+比值（4.30±2.28）与宫内感染组的（4.75±3.23）比较，差异尚不能认为有统计学意义（t=-0.30,P=0.767）。
④非宫内感染组的mDC的百分比（0.84±0.58）高于宫内感染组（0.67±0.34），差异尚不能认为有统计学意义（t=-0.485,P=0.633）；非宫内感染组的pDC（0.92±0.91）与宫内感染组的（0.91±0.46）比较，差异没有统计学意义（t=0.020,P=0.984）。
⑤非宫内感染组的CD4~+CD25~+Treg细胞的百分比（4.69±3.41）与宫内感染组（3.00）比较，差异无统计学意义（t=0.474,P=0.646）。
结论
①非宫内感染组的TLR3蛋白表达平均荧光强度值高于宫内感染组，而宫内感染组经PolyI:C刺激后其表达水平升高，提示宫内感染可能与婴儿TLR3表达有关。
②非宫内感染组的B细胞、CD4~+T细胞、mDC的百分比高于宫内感染组，提示宫内感染与婴儿B细胞、CD4~+T细胞、mDC表达可能有关。
③本次研究未发现宫内感染与CD8~+T细胞、pDC、CD4~+CD25+Treg细胞的百分比以及CD4~+/CD8~+比值相关，有待于进一步研究。
OBJECTIVE:
①To investigate the relationship between TLR3 in the PBMC of the unbilicalvein blood of babies whose mothers are HBsAg posotive and HBV intrauterineinfection.
②To explore the relationship between immunocytes concerning PBMC and theHBV intrauterine infection.
③To explore the mechanism of TLR3 in HBV intrauterine infection .
METHODS:
①The epidemiological base line data and umbilical vein blood of 52HBsAg-positive pregnant women were collected from Taiyuan infectious hospitalfrom July 2011 to January 2012.
②Experiment was performed in vitro: The PBMC were separated from umbilicalvein blood and then were cultured. The PBMC of HBV intrauterine infection wereintervented by HBV+PolyI:C and HBV.The PBMC with negative HBV intrauterineinfection were intervented only by HBV.
③The protein expession of TLR3 and the percentages of B-cells,T-cells,DC andTreg were detected by FCM.
RESULTS:
①The expression level of TLR3 protein was higher in PBMC with negativeHBV intrauterine infection than that in PBMC with positive HBV intrauterineinfection(32.18±11.36,30.29±11.04),but no significant difference was observed（t=0.410，P=0.684）.After the intervention of PolyI:C, the expression level of TLR3increased,but still no significant difference was observed (32.18±11.36, 32.16±9.40;t=-1.824,P=0.078).
②Proportion of B-cells with negative HBV intrauterine uninfection was higherthan the ones with positive HBV intrauterine infection(7.38±6.40;6.76±4.01),but nosignificant difference was observed (t=0.210,P=0.834).After the intervention ofPolyI:C, percentage of B-cells with positive HBV intrauterine uninfection decreased,but still no significant difference was observed(7.38±6.40,5.14±2.64;t=0.768,P=0.447).
③Percentage of CD4+T-cells with negative HBV intrauterine infection washigher than the ones with positive HBV intrauterine infection,but no significantdifference was observed(41.14±20.08,33.82±2.60;t=0.618,P=0.543),while percentageof CD8+T-cells with negative HBV intrauterine infection was higher than the oneswith positive HBV intrauterine infection(11.30±5.87,11.14±9.64) with no significantdifference(11.30±5.87,11.14±9.64;t=0.041,P=0.968).The difference of ratio ofCD4+T-cells to CD8+T-cells between negative and positive HBV intrauterine infectiongroups was not significant(4.30±2.28,4.75±3.23;t=-0.30,P=0.767).
④Percentage of mDC with negaitive HBV intrauterine infection was higher thanthe one with positive HBV intrauterine infection(0.84±0.58,0.67±0.34) but with nosignificant difference (t=-0.485,P=0.633).While percentage of pDC with negaitiveHBV intrauterine infection was higher than the one with positive HBV intrauterineinfection,but with no significant difference there was(0.92±0.91,0.91±0.46;t=0.020,P=0.984).
⑤Percentage of CD4+CD25+Treg with negative HBV intrauterine infection washigher than the one with positive HBV intrauterine infection(4.69±3.41,3.00),but withno significant difference between them(t=0.474,P=0.646).
CONCLUSIONS:
①The fact that expression level of TLR3 protein with negative HBVintrauterine infection was higher than the one with HBV intrauterine infection andthat intervention of PolyI:C caused the increase of the expression level of TLR3protein indicates that HBV intrauterine infection may be linked to TLR3 proteinexpresson.
②The fact that the percentages of B-cells,CD4+T-cells and mDC with negativeHBV intrauterine infection were higher than the ones with positive intrauterineinfection indicates that the B-cells,CD4+T-cells,mDC may be a protective factoragainst placenta HBV infection.
③The fact that association between percentage of CD8+T-cells,pDC as well asCD4+CD25+Treg and the CD4+/CD8+T-cells was not discovered indicates that furtherstudy is required.
引文
[1]Maddrey WC.Hepatitis B:an important public health issue.J Med Virol,2000,61(3):362-366
[2]Hou, J., Z. Liu, and F. Gu.. Epidemiology and prevention of hepatitis B virus infection. Int. J.Med. Sci. ,2005 ,2:50–57
[3]MedzhitovR.Toll-like receptors and innate immunity.NatureRev.Immunology,2001,1:135-145
[4]Akira S,Takeda K. Toll-like receptor signalling. Nat Rev Immunol, 2004,4(7):499-511
[5]Sanghavi SK, Reinhart TA. Increased expression of TLR3 in lymph nodes during simianimmunodeficiency virus infection: implication for inflammation and immunodeficiency. JImmunol,2005 Oct 15;175(8):5314-5323
[6] Seki, E.and D. A. Brenner. Toll-like receptors and adaptor molecules in liver disease:update.Hepatology ,2008.48:322–335
[7]Mencin, A., J. Kluwe, and R. F. Schwabe.Toll-like receptors as targets in chronic liver diseases.Gut, 2009, 58:704–720
[8]Nicole C Stowell, Jonathan Seideman, Holly A Raymond,et al. Long-term activation of TLR3by Poly(I:C) induces inflammation and impairs lung function in mice. RespiratoryResearch,2009,10(43):1-14
[9]Negishi, H, T. Osawa, K. Ogami, X,et al.. A critical link between Toll-like receptor 3 and typeII interferon signaling pathways in antiviral innate immunity. Proc. Natl. Acad.Sci.,2008,105:20446–20451
[10]Salem, ML, El-Naggar SA, Kadima A, et al. The adjuvant effects of the toll-like receptor 3ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8+T cell responses arepartially dependent on NK cells with the induction of a beneficial cytokine milieu.Vaccine,2006,24:5119–5132
[11]Trumpfheller C, Caskey M, Nchinda G, et al. The microbial mimic polyI:C induces durableand protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc. Natl.Acad. Sci. USA., 2008,105:2574–2579
[12]Stahl-Hennig C, Eisenblatter M, Jasny E, et al. Synthetic double-stranded RNAs are adjuvantsfor the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesusmacaques. PLoS Pathog,2009,5:e1000373
[13]Blanco P, Palucka AK,Gill M, et al. Induction of dendritic cell differentiation by IFN- insystemic lupus erythematosus. Science,2001,294:1540–1543
[14]Luft T,Pang KC,Thomas E, et al. Type I IFNs enhance the terminal differentiation of dendriticcells. J. Immunol,1998,161:1947–1953
[15]Gallucci S, Lolkema M, Matzinger P. Natural adjuvants: endogenous activators of dendriticcells. Nat. Med., 1999,5:1249–1255
[16]Le Bon A, Etchart N, Rossmann C, et al. Cross-priming of CD8+T cells stimulated byvirus-induced type I interferon. Nat. Immunol,2003, 4:1009–1015
[17]Kolumam GA, Thomas S, Thompson LJ, et al. Type I interferons act directly on CD8+T cellsto allow clonal expansion and memory formation in response to viral infection. J Exp Med. 2005,202:637–650
[18]Le Bon A, Durand V, KamphuisE, et al. Direct stimulation of T cells by type I IFN enhancesthe CD8+T cell response during crosspriming. J. Immunol,2006,176:4682–4689
[19]Longhi MP, Trumpfheller C, Idoyaga J, et al. Dendritic cells require a systemic type Iinterferon response to mature and induce CD4+Th1 immunity with poly I:C as adjuvant. J. Exp.Med.,2009, 206 (7): 1589-1602
[20]胡婷.TLR3与胎盘细胞凋亡在胎盘HBV感染及HBV宫内感染中的作用：[硕士学位论文].太原:山西医科大学,2010
[21]李淑珍,王素萍,原深利,等.孕妇HBV感染与胎盘组织TLR3表达关系[J].中国公共卫生.2008,24(2):129-130
[22]李小燕.TOLL样受体在乙肝病毒致BEWO细胞凋亡中的作用:[硕士学位论文]太原:山西医科大学,2009
[23]宋秀霞.Toll样受体3与HBV感染和HBV宫内感染的关系及其作用机制的研究:博士学位论文].太原:山西医科大学,2008
[23]原琛利.胎盘组织TLR3分布与胎盘HBV感染及HBV宫内感染的关系研究:[硕士学位论文].太原:山西医科大学,2006
[25]Medzhitov R．Toll-like receptors and innate immunity．Nat Rev Immunol，2001,1:135－45
[26]陈明泉.HBV DNA载量、Toll样受体3的表达变化与慢性乙型病毒性肝炎患者外周血树突状细胞表型、功能的相关性研究:[硕士学位论文].上海:复旦大学.2006
[27]Alexopoulou L,Holt AC,Medzhitov R,et al.Recognition of double-stranded RNA andactivation of NF-kappaB by Toll-like receptor 3 [J].Nature,2001,413 (6857):32-738
[28]Verdijk R M,Mutis T,Esendam B,et al.Polyriboinosinic polyribo-cytidylic acid[PolyI:C]induces stable maturation of functionally active human dendritic cells [J].J Immunol,1999,163(1):57-61
[29]Fujimoto C,Nakagawa Y,Ohara K,et al.Polyriboinosinic polyribo-cytidylic acid [poly (I:C)]/TLR3 signaling allows class I processing of exogenous protein and induction of HIV-specificCD8 +cytotoxic Tlymphocytes [J].Int Immunol,2004,16(1):55-63
[30]Zhu Q, Egelston C, Gagnon S，et al. Using 3 TLR ligands as a combination adjuvant inducesqualitative changes in T cell responses needed for antiviral protection in mice[J]. J ClinInvest,2010,120(2):607–616
[31]吴引伟等.慢性乙型肝炎患者外周血B淋巴细胞及其活化状况研究[J].山东医药,2005,45(31):1-3
[32]Roitt L，Bmstoff J，Male D．免疫学[M]．6版．(周光炎，译)．北京：人民卫生出版社，2002：53-56
[33]王敏，王福生，刘敬超．慢性乙型肝炎患者外周血淋巴细胞亚群与病程相关性的研究[J]．肝脏，2003，8(2):18—20
[34]陆得源．现代免疫学EM[J].上海:上海科学技术出版社,1995,129-131
[35]王芳.乙肝病毒感染孕妇分娩婴幼儿联合免疫失败机制的研究:[硕士学位论文].泰安:泰山医学院.2009
[36]鞠平平，余敏敏等.乙肝病毒宫内感染免疫失败机制的探讨[J].实用妇产科杂志,2010,26(8):625-628
[37]杜二球，郑九生.新生儿HBV宫内感染脐血T淋巴细胞亚群的特点[J].江西医学院学报，2009,49(2):55-58
[38]Beckebaum S , Cicinnati VR , Zhang X, et al . Hepatitis B virus-induecd defect ofmonocyte-derived dendritic cells leads to impaired T helper type1 response in vitro , mechanismsfor viral immune escape. Immunology ,2003 , 109 : 487-495
[39]Chisari FV , Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol ,1995 , 13 :29-60
[40]吕晴，朱启镕，熊恩东，等．对宫内乙型肝炎病毒感染婴儿特异性杀伤性T淋巴细胞功能的探讨[J]．中华儿科杂志,1998,36(5):305-306
[41]Sato K,Kawasaka H,Nagayama H,et al.TGF bena-1 reciprocally controls chomotaxis ofhuman peripheral blood monocytc-derived dendritic cells via chemokine receptors. JImmunol,2000,164:2285-2295
[42] Liu YJ . Dendritic cells subsets and lineages , and their functions in innate and adaptiveimmunity. Cell ,2001 , 106 : 259-262
[43]Beckebaum S , Cicinnati VR , Dworacki G, et al . Reduction in the circulating MDC/PDCratio and impaired function of ex vivo-generated DC1 in chronic hepatitis B infection. ClinicalImmunology ,2002 , 104 : 138-150
[44]王琦等.CD4+CD25+Treg细胞对B细胞的作用机制分析[J].中国免疫学杂志,2008,24(5)：387-390
[45]Nakamura K，Kitani A，Strober W．Cell contact deoendent immunosuppression byCD4+CD25+regulatory T cells is mediated by cell surface-bound transforming growth factorbeta[J].J Exp Med.,2001,194(5)：629-644
[46]Jemieson B D,Ahmed R.T-cell tolorance：exposure to virus in utero does not cause apermanent deletion of a specific T cells[J].Proc NatlAcad Sci USA,1988,85(7):2265-2268
[47]Wang Z,Zhang J,Yang H,et al.Quantitative analysis of HBV DNA level and HBeAg titer inhepatitis B surface antigen positive mothers and their babies：HBeAg passage through theplacenta and the rate of decay in babies[J].J Med Viral ,2003,71(3):360-366
[48]Wang J S,Zhu Q R.Infection of the fetus with hepatitis B e antigen via theplacenta[J].Lancent,2000,355(9208):989
[49]施可庆.慢性乙型肝炎病毒感染产妇的新生儿脐带血CD4+CD25+调节性T细胞的频数分析:[硕士学位论文].重庆:重庆医科大学.2008
[1]Medzhitov R. Toll-like receptors and innate immunity. Nature Rev. Immunology,2001,1:135—145
[2] Medzhitov R，Janeway Jr CA.Innate immunity:the virtues of a nonclonal system ofrecognition．Cell，1997，91：295—298
[3] Medzhitov R. Toll-like receptors and innate immunity.Nat Rev Immunol，2001,1:135—145
[4]K. Takeda, T. Kaisho and S. Akira.Toll-like receptors.Annu Rev Immunol ,2003 (21):335–376
[5]D. Zhang, G. Zhang, M.S. Hayden, M.B. Greenblatt, C. Bussey and R.A. Flavell et al.,Atoll-like receptor that prevents infection by uropathogenic bacteria.Science,2004(303): 1522–1526
[6]Sanghavi SK, Reinhart TA. Increased expression of TLR3 in lymph nodes during simianimmune deficiency virus infection: implication for inflammation and immune deficiency.JImmunol,2005 Oct 15,175（8）:5314—5323
[7]Rock F L,Hardiman G,Timans J C,et al.Developmental Biology:A family of human receptorsstructurally related to Drosophila Toll[J]. Proc Natl Acad Sci USA,1998,95(2):588—593
[8]Takeda K,Kaisho T,Akira S.Toll-like receptors[J].Annu Rev Immunol,2003,21:335-376
[9]金丹，吕凤林. TLR3免疫识别dsRNA病毒的分子机制[J].病毒学报,2005,21(2):155-159
[10]F.L. Rock, G. Hardiman,J.C. Timans,et al.A family of human receptors structurally related toDrosophila Toll. Proc. Natl.Acad.Sci.U.S.A. ,1998,95: 588–593
[11]E. Cario, D.K. Podolsky.Differential alteration in intestinal epithelial cell expression ofToll-like receptor 3(TLR3) and TLR4 in inflammatory bowel disease. Immun. 2000,68:7010–7017
[12]M. Muzio,D. Bosisio,N. Polentarutti,et al.Differential expression and regulation of Toll-likereceptors(TLR) in human leukocytes: selective expression of TLR3 in dendriticcells[J].Immunol.2000,64:5998–6004
[13]A. Visintin,A. Mazzoni, J.H. Spitzer,D.H. Wyllie,et al.Regulation of Toll-like receptors inhuman monocytes and dendritic cells[J].Immunol,2001,166: 249–254
[14]Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family.Immunol Lett, 2003, 85:85—95
[15]Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol, 2002,20:709-760
[16]Hu X.et al.Multimerization on and interaetion of Toll and SP atzle in Drosophila.ProeNatlAcad Sci USA，2004,101(25):9369—9374
[17]Alexopoulou L，Holt A C，Medzhitov R.,et a1．Recognition of double-stranded RNA andactivation of NF kappa B by Toll—like receptor 3[J]．Nature，2001，413(6857)：732—738
[18]Zhang F X，Kirschning C J，Mancinelli R，et a1．Bacterial lipopolysaccharide activates nuclearfactor kappa B through inter-leukin--signaling mediators in cultured human dermal endothelialcells and mononuclear phagocytes[J]．J Biol Chem.,1999 Mar 19,274(12):7611—4
[19]Takeuchi O,Sato S,Horiuchi,et al. Cutting edge: role of Toll-like receptor 1 inmediating immune response to microbial lipoproteins. J Immunol ,2002, 169:10—14
[20]Sato S，Sugiyama M，Yamamoto M，et a1．Toll／IL- 1 receptor domain containing adaptorinducing IFN beta(TRIF) associates with TNF receptor associated factor 6 and TANK bindingkinase 1，and activates two distinct transcription factors，NF kappa B and IFN regulatory factor-3，in the Toll like receptor signaling[J].J Immunol，2003，171(8)：4304—4310
[21]Yamamoto M，Sato S，Hemmi H，et a1．Role of Adaptor TRIF in the MyD88 Independent TollLike Receptor Signaling Pathway[J]．Science，2003，301(5633)：640—643
[22] Akira S,Uematsu S,Takeuchi O.Pathogen recognition and innate immunity[J].Cell,2006，124(4):783-801
[23]van Duin D，Medzhitov R，Shaw A C．Triggering TLR signaling in vaccination[J]．TrendsImmunol，2006，27(1)：49—55
[24]徐德忠,闫永平,徐剑秋,等.乙型肝炎病毒宫内传播因素和机制的分子流行病学研究[J].中华医学杂志,1999,79(1):24-27.
[25]魏俊妮,王素萍,双杰玉.母胎细胞转运与乙肝病毒宫内感染关系的研究.中华流行病学杂志,2005,26(4):240-244
[26]李铁钢,王素萍,李淑珍,等.HBsAg阳性孕妇胎盘HBV感染状况及危险因素[J].中国公共卫生,2005,21(2):165-166
[27]李淑珍.TLR3在人类胎盘HBV感染中作用的研究:[博士学位论文].太原:山西医科大学,2008
[28]李小燕.TOLL样受体在乙肝病毒致BEWO细胞凋亡中的作用:[硕士学位论文]太原:山西医科大学,2009
[29]原深利.胎盘组织TLR3分布与胎盘HBV感染及宫内感染的关系研究:[硕士学位论文]太原:山西医科大学,2006
[30]Han Bai,Lin Zhang,Li Ma,et al.Relationship of hapatitis B virus infetion of placental barrierand hepatitis B virus intra-uterine transmissin mechanism.World Journal of Castroenterology,2007July 14,13(26):3625—3630
[31]原深利,王素萍,宋秀霞.胎盘HBV感染的危险因素及与TLR3的关系研究[J].山西医科大学,2006,37(5):514-516
[32]车小文,王素萍,李淑珍,等.实时荧光定量PCR检测HBsAg阳性孕妇胎盘组织TLR3的表达[J].现代预防医学,2006,35(9):1686-1687
[33]李淑珍,王素萍,原深利,等.孕妇HBV感染与胎盘组织TLR3表达关系[J].中国公共卫生.2008,24(2):129-130
[34]阎娟.TLR3及其相关细胞因子在Bewo细胞抗HBV感染作用的研究:[硕士学位论文].太原：山西医科大学，2010
[35]白函,张琳,何丽霞,等.世界华人消化杂志.胎盘滋养层细胞的感染和凋亡与HBV宫内传播机制.2007,15(15):1695-1700
[36]胡婷.TLR3与胎盘细胞凋亡在胎盘HBV感染及HBV宫内感染中的作用:[硕士学位论文].太原：山西医科大学，2010
[37]宋秀霞.TOLL样受体与HBV感染和宫内感染的关系及其作用机制的研究:[博士学位论文].太原:山西医科大学,2008
[38]王建设,朱启镕．宫腔感染乙肝肝炎病毒免疫失败儿童Thl型和Th2型细胞因子研究[J]．中华儿科杂志，2002，40(8)：481—484
[39]Choong M I,Ton S H,Cheong S K ,et a1.The Cellular Immune Status of HBsAg-postiveCarriers in Malaysia[J]．Asian Pac JAllergy Immuol，1996，14(1)：19—24
[40]杜二球，郑九生.新生儿HBV宫内感染脐血T淋巴细胞亚群的特点[J].江西医学院学报.2009,49(2):55-58
[41]朱启镕，吕晴，俞蕙，等．宫内感染HBV婴儿接种乙肝疫苗免疫失败的机制和预后研究[J]．中华儿科杂志，1997，35(7)：349-352
[42]吕晴，朱启镕，熊恩东，等．对宫内乙型肝炎病毒感染婴儿特异性杀伤性T淋巴细胞功能的探讨[J]．中华儿科杂志，1998，36(5)：305-306
[43]余敏敏，韩国荣，王建芳.新生儿宫内感染乙型肝炎病毒后T淋巴细胞亚群的变化[J].中国实用妇科与产科杂志.2006,5,22(5):364-366
[44]施可庆.慢性乙型肝炎病毒感染产妇的新生儿脐带血CD4+CD25+调节性T细胞的频数分析:[硕士学位论文].重庆：重庆医科大学.2008
[45]Sacks，D&Noben-Trauth,N．The immunology of susceptibility and resistance toLeishmaniamajor in mice[J]．Nat.Rev.Immune,2002,2:845—858
[46]]Aseffa,A.et al.The early IL-4 response to Leishmania major and the resulting Th2cellmaturation steering progressive disease in BALB/c mice are subject to the control ofregulatory CD4+CD25+T cells[J].J.Immunol,2002,169:3232—3241
[47]马奔,李霄等.树突状细胞和CD4+CD25+调节性T细胞在免疫耐受中的作用及关系.国际外科学杂志,2011,2,38(2):124-127
[2]Hou, J., Z. Liu, and F. Gu.. Epidemiology and prevention of hepatitis B virus infection. Int. J.Med. Sci. ,2005 ,2:50–57
[3]MedzhitovR.Toll-like receptors and innate immunity.NatureRev.Immunology,2001,1:135-145
[4]Akira S,Takeda K. Toll-like receptor signalling. Nat Rev Immunol, 2004,4(7):499-511
[5]Sanghavi SK, Reinhart TA. Increased expression of TLR3 in lymph nodes during simianimmunodeficiency virus infection: implication for inflammation and immunodeficiency. JImmunol,2005 Oct 15;175(8):5314-5323
[6] Seki, E.and D. A. Brenner. Toll-like receptors and adaptor molecules in liver disease:update.Hepatology ,2008.48:322–335
[7]Mencin, A., J. Kluwe, and R. F. Schwabe.Toll-like receptors as targets in chronic liver diseases.Gut, 2009, 58:704–720
[8]Nicole C Stowell, Jonathan Seideman, Holly A Raymond,et al. Long-term activation of TLR3by Poly(I:C) induces inflammation and impairs lung function in mice. RespiratoryResearch,2009,10(43):1-14
[9]Negishi, H, T. Osawa, K. Ogami, X,et al.. A critical link between Toll-like receptor 3 and typeII interferon signaling pathways in antiviral innate immunity. Proc. Natl. Acad.Sci.,2008,105:20446–20451
[10]Salem, ML, El-Naggar SA, Kadima A, et al. The adjuvant effects of the toll-like receptor 3ligand polyinosinic-cytidylic acid poly (I:C) on antigen-specific CD8+T cell responses arepartially dependent on NK cells with the induction of a beneficial cytokine milieu.Vaccine,2006,24:5119–5132
[11]Trumpfheller C, Caskey M, Nchinda G, et al. The microbial mimic polyI:C induces durableand protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc. Natl.Acad. Sci. USA., 2008,105:2574–2579
[12]Stahl-Hennig C, Eisenblatter M, Jasny E, et al. Synthetic double-stranded RNAs are adjuvantsfor the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesusmacaques. PLoS Pathog,2009,5:e1000373
[13]Blanco P, Palucka AK,Gill M, et al. Induction of dendritic cell differentiation by IFN- insystemic lupus erythematosus. Science,2001,294:1540–1543
[14]Luft T,Pang KC,Thomas E, et al. Type I IFNs enhance the terminal differentiation of dendriticcells. J. Immunol,1998,161:1947–1953
[15]Gallucci S, Lolkema M, Matzinger P. Natural adjuvants: endogenous activators of dendriticcells. Nat. Med., 1999,5:1249–1255
[16]Le Bon A, Etchart N, Rossmann C, et al. Cross-priming of CD8+T cells stimulated byvirus-induced type I interferon. Nat. Immunol,2003, 4:1009–1015
[17]Kolumam GA, Thomas S, Thompson LJ, et al. Type I interferons act directly on CD8+T cellsto allow clonal expansion and memory formation in response to viral infection. J Exp Med. 2005,202:637–650
[18]Le Bon A, Durand V, KamphuisE, et al. Direct stimulation of T cells by type I IFN enhancesthe CD8+T cell response during crosspriming. J. Immunol,2006,176:4682–4689
[19]Longhi MP, Trumpfheller C, Idoyaga J, et al. Dendritic cells require a systemic type Iinterferon response to mature and induce CD4+Th1 immunity with poly I:C as adjuvant. J. Exp.Med.,2009, 206 (7): 1589-1602
[20]胡婷.TLR3与胎盘细胞凋亡在胎盘HBV感染及HBV宫内感染中的作用：[硕士学位论文].太原:山西医科大学,2010
[21]李淑珍,王素萍,原深利,等.孕妇HBV感染与胎盘组织TLR3表达关系[J].中国公共卫生.2008,24(2):129-130
[22]李小燕.TOLL样受体在乙肝病毒致BEWO细胞凋亡中的作用:[硕士学位论文]太原:山西医科大学,2009
[23]宋秀霞.Toll样受体3与HBV感染和HBV宫内感染的关系及其作用机制的研究:博士学位论文].太原:山西医科大学,2008
[23]原琛利.胎盘组织TLR3分布与胎盘HBV感染及HBV宫内感染的关系研究:[硕士学位论文].太原:山西医科大学,2006
[25]Medzhitov R．Toll-like receptors and innate immunity．Nat Rev Immunol，2001,1:135－45
[26]陈明泉.HBV DNA载量、Toll样受体3的表达变化与慢性乙型病毒性肝炎患者外周血树突状细胞表型、功能的相关性研究:[硕士学位论文].上海:复旦大学.2006
[27]Alexopoulou L,Holt AC,Medzhitov R,et al.Recognition of double-stranded RNA andactivation of NF-kappaB by Toll-like receptor 3 [J].Nature,2001,413 (6857):32-738
[28]Verdijk R M,Mutis T,Esendam B,et al.Polyriboinosinic polyribo-cytidylic acid[PolyI:C]induces stable maturation of functionally active human dendritic cells [J].J Immunol,1999,163(1):57-61
[29]Fujimoto C,Nakagawa Y,Ohara K,et al.Polyriboinosinic polyribo-cytidylic acid [poly (I:C)]/TLR3 signaling allows class I processing of exogenous protein and induction of HIV-specificCD8 +cytotoxic Tlymphocytes [J].Int Immunol,2004,16(1):55-63
[30]Zhu Q, Egelston C, Gagnon S，et al. Using 3 TLR ligands as a combination adjuvant inducesqualitative changes in T cell responses needed for antiviral protection in mice[J]. J ClinInvest,2010,120(2):607–616
[31]吴引伟等.慢性乙型肝炎患者外周血B淋巴细胞及其活化状况研究[J].山东医药,2005,45(31):1-3
[32]Roitt L，Bmstoff J，Male D．免疫学[M]．6版．(周光炎，译)．北京：人民卫生出版社，2002：53-56
[33]王敏，王福生，刘敬超．慢性乙型肝炎患者外周血淋巴细胞亚群与病程相关性的研究[J]．肝脏，2003，8(2):18—20
[34]陆得源．现代免疫学EM[J].上海:上海科学技术出版社,1995,129-131
[35]王芳.乙肝病毒感染孕妇分娩婴幼儿联合免疫失败机制的研究:[硕士学位论文].泰安:泰山医学院.2009
[36]鞠平平，余敏敏等.乙肝病毒宫内感染免疫失败机制的探讨[J].实用妇产科杂志,2010,26(8):625-628
[37]杜二球，郑九生.新生儿HBV宫内感染脐血T淋巴细胞亚群的特点[J].江西医学院学报，2009,49(2):55-58
[38]Beckebaum S , Cicinnati VR , Zhang X, et al . Hepatitis B virus-induecd defect ofmonocyte-derived dendritic cells leads to impaired T helper type1 response in vitro , mechanismsfor viral immune escape. Immunology ,2003 , 109 : 487-495
[39]Chisari FV , Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol ,1995 , 13 :29-60
[40]吕晴，朱启镕，熊恩东，等．对宫内乙型肝炎病毒感染婴儿特异性杀伤性T淋巴细胞功能的探讨[J]．中华儿科杂志,1998,36(5):305-306
[41]Sato K,Kawasaka H,Nagayama H,et al.TGF bena-1 reciprocally controls chomotaxis ofhuman peripheral blood monocytc-derived dendritic cells via chemokine receptors. JImmunol,2000,164:2285-2295
[42] Liu YJ . Dendritic cells subsets and lineages , and their functions in innate and adaptiveimmunity. Cell ,2001 , 106 : 259-262
[43]Beckebaum S , Cicinnati VR , Dworacki G, et al . Reduction in the circulating MDC/PDCratio and impaired function of ex vivo-generated DC1 in chronic hepatitis B infection. ClinicalImmunology ,2002 , 104 : 138-150
[44]王琦等.CD4+CD25+Treg细胞对B细胞的作用机制分析[J].中国免疫学杂志,2008,24(5)：387-390
[45]Nakamura K，Kitani A，Strober W．Cell contact deoendent immunosuppression byCD4+CD25+regulatory T cells is mediated by cell surface-bound transforming growth factorbeta[J].J Exp Med.,2001,194(5)：629-644
[46]Jemieson B D,Ahmed R.T-cell tolorance：exposure to virus in utero does not cause apermanent deletion of a specific T cells[J].Proc NatlAcad Sci USA,1988,85(7):2265-2268
[47]Wang Z,Zhang J,Yang H,et al.Quantitative analysis of HBV DNA level and HBeAg titer inhepatitis B surface antigen positive mothers and their babies：HBeAg passage through theplacenta and the rate of decay in babies[J].J Med Viral ,2003,71(3):360-366
[48]Wang J S,Zhu Q R.Infection of the fetus with hepatitis B e antigen via theplacenta[J].Lancent,2000,355(9208):989
[49]施可庆.慢性乙型肝炎病毒感染产妇的新生儿脐带血CD4+CD25+调节性T细胞的频数分析:[硕士学位论文].重庆:重庆医科大学.2008
[1]Medzhitov R. Toll-like receptors and innate immunity. Nature Rev. Immunology,2001,1:135—145
[2] Medzhitov R，Janeway Jr CA.Innate immunity:the virtues of a nonclonal system ofrecognition．Cell，1997，91：295—298
[3] Medzhitov R. Toll-like receptors and innate immunity.Nat Rev Immunol，2001,1:135—145
[4]K. Takeda, T. Kaisho and S. Akira.Toll-like receptors.Annu Rev Immunol ,2003 (21):335–376
[5]D. Zhang, G. Zhang, M.S. Hayden, M.B. Greenblatt, C. Bussey and R.A. Flavell et al.,Atoll-like receptor that prevents infection by uropathogenic bacteria.Science,2004(303): 1522–1526
[6]Sanghavi SK, Reinhart TA. Increased expression of TLR3 in lymph nodes during simianimmune deficiency virus infection: implication for inflammation and immune deficiency.JImmunol,2005 Oct 15,175（8）:5314—5323
[7]Rock F L,Hardiman G,Timans J C,et al.Developmental Biology:A family of human receptorsstructurally related to Drosophila Toll[J]. Proc Natl Acad Sci USA,1998,95(2):588—593
[8]Takeda K,Kaisho T,Akira S.Toll-like receptors[J].Annu Rev Immunol,2003,21:335-376
[9]金丹，吕凤林. TLR3免疫识别dsRNA病毒的分子机制[J].病毒学报,2005,21(2):155-159
[10]F.L. Rock, G. Hardiman,J.C. Timans,et al.A family of human receptors structurally related toDrosophila Toll. Proc. Natl.Acad.Sci.U.S.A. ,1998,95: 588–593
[11]E. Cario, D.K. Podolsky.Differential alteration in intestinal epithelial cell expression ofToll-like receptor 3(TLR3) and TLR4 in inflammatory bowel disease. Immun. 2000,68:7010–7017
[12]M. Muzio,D. Bosisio,N. Polentarutti,et al.Differential expression and regulation of Toll-likereceptors(TLR) in human leukocytes: selective expression of TLR3 in dendriticcells[J].Immunol.2000,64:5998–6004
[13]A. Visintin,A. Mazzoni, J.H. Spitzer,D.H. Wyllie,et al.Regulation of Toll-like receptors inhuman monocytes and dendritic cells[J].Immunol,2001,166: 249–254
[14]Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family.Immunol Lett, 2003, 85:85—95
[15]Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol, 2002,20:709-760
[16]Hu X.et al.Multimerization on and interaetion of Toll and SP atzle in Drosophila.ProeNatlAcad Sci USA，2004,101(25):9369—9374
[17]Alexopoulou L，Holt A C，Medzhitov R.,et a1．Recognition of double-stranded RNA andactivation of NF kappa B by Toll—like receptor 3[J]．Nature，2001，413(6857)：732—738
[18]Zhang F X，Kirschning C J，Mancinelli R，et a1．Bacterial lipopolysaccharide activates nuclearfactor kappa B through inter-leukin--signaling mediators in cultured human dermal endothelialcells and mononuclear phagocytes[J]．J Biol Chem.,1999 Mar 19,274(12):7611—4
[19]Takeuchi O,Sato S,Horiuchi,et al. Cutting edge: role of Toll-like receptor 1 inmediating immune response to microbial lipoproteins. J Immunol ,2002, 169:10—14
[20]Sato S，Sugiyama M，Yamamoto M，et a1．Toll／IL- 1 receptor domain containing adaptorinducing IFN beta(TRIF) associates with TNF receptor associated factor 6 and TANK bindingkinase 1，and activates two distinct transcription factors，NF kappa B and IFN regulatory factor-3，in the Toll like receptor signaling[J].J Immunol，2003，171(8)：4304—4310
[21]Yamamoto M，Sato S，Hemmi H，et a1．Role of Adaptor TRIF in the MyD88 Independent TollLike Receptor Signaling Pathway[J]．Science，2003，301(5633)：640—643
[22] Akira S,Uematsu S,Takeuchi O.Pathogen recognition and innate immunity[J].Cell,2006，124(4):783-801
[23]van Duin D，Medzhitov R，Shaw A C．Triggering TLR signaling in vaccination[J]．TrendsImmunol，2006，27(1)：49—55
[24]徐德忠,闫永平,徐剑秋,等.乙型肝炎病毒宫内传播因素和机制的分子流行病学研究[J].中华医学杂志,1999,79(1):24-27.
[25]魏俊妮,王素萍,双杰玉.母胎细胞转运与乙肝病毒宫内感染关系的研究.中华流行病学杂志,2005,26(4):240-244
[26]李铁钢,王素萍,李淑珍,等.HBsAg阳性孕妇胎盘HBV感染状况及危险因素[J].中国公共卫生,2005,21(2):165-166
[27]李淑珍.TLR3在人类胎盘HBV感染中作用的研究:[博士学位论文].太原:山西医科大学,2008
[28]李小燕.TOLL样受体在乙肝病毒致BEWO细胞凋亡中的作用:[硕士学位论文]太原:山西医科大学,2009
[29]原深利.胎盘组织TLR3分布与胎盘HBV感染及宫内感染的关系研究:[硕士学位论文]太原:山西医科大学,2006
[30]Han Bai,Lin Zhang,Li Ma,et al.Relationship of hapatitis B virus infetion of placental barrierand hepatitis B virus intra-uterine transmissin mechanism.World Journal of Castroenterology,2007July 14,13(26):3625—3630
[31]原深利,王素萍,宋秀霞.胎盘HBV感染的危险因素及与TLR3的关系研究[J].山西医科大学,2006,37(5):514-516
[32]车小文,王素萍,李淑珍,等.实时荧光定量PCR检测HBsAg阳性孕妇胎盘组织TLR3的表达[J].现代预防医学,2006,35(9):1686-1687
[33]李淑珍,王素萍,原深利,等.孕妇HBV感染与胎盘组织TLR3表达关系[J].中国公共卫生.2008,24(2):129-130
[34]阎娟.TLR3及其相关细胞因子在Bewo细胞抗HBV感染作用的研究:[硕士学位论文].太原：山西医科大学，2010
[35]白函,张琳,何丽霞,等.世界华人消化杂志.胎盘滋养层细胞的感染和凋亡与HBV宫内传播机制.2007,15(15):1695-1700
[36]胡婷.TLR3与胎盘细胞凋亡在胎盘HBV感染及HBV宫内感染中的作用:[硕士学位论文].太原：山西医科大学，2010
[37]宋秀霞.TOLL样受体与HBV感染和宫内感染的关系及其作用机制的研究:[博士学位论文].太原:山西医科大学,2008
[38]王建设,朱启镕．宫腔感染乙肝肝炎病毒免疫失败儿童Thl型和Th2型细胞因子研究[J]．中华儿科杂志，2002，40(8)：481—484
[39]Choong M I,Ton S H,Cheong S K ,et a1.The Cellular Immune Status of HBsAg-postiveCarriers in Malaysia[J]．Asian Pac JAllergy Immuol，1996，14(1)：19—24
[40]杜二球，郑九生.新生儿HBV宫内感染脐血T淋巴细胞亚群的特点[J].江西医学院学报.2009,49(2):55-58
[41]朱启镕，吕晴，俞蕙，等．宫内感染HBV婴儿接种乙肝疫苗免疫失败的机制和预后研究[J]．中华儿科杂志，1997，35(7)：349-352
[42]吕晴，朱启镕，熊恩东，等．对宫内乙型肝炎病毒感染婴儿特异性杀伤性T淋巴细胞功能的探讨[J]．中华儿科杂志，1998，36(5)：305-306
[43]余敏敏，韩国荣，王建芳.新生儿宫内感染乙型肝炎病毒后T淋巴细胞亚群的变化[J].中国实用妇科与产科杂志.2006,5,22(5):364-366
[44]施可庆.慢性乙型肝炎病毒感染产妇的新生儿脐带血CD4+CD25+调节性T细胞的频数分析:[硕士学位论文].重庆：重庆医科大学.2008
[45]Sacks，D&Noben-Trauth,N．The immunology of susceptibility and resistance toLeishmaniamajor in mice[J]．Nat.Rev.Immune,2002,2:845—858
[46]]Aseffa,A.et al.The early IL-4 response to Leishmania major and the resulting Th2cellmaturation steering progressive disease in BALB/c mice are subject to the control ofregulatory CD4+CD25+T cells[J].J.Immunol,2002,169:3232—3241
[47]马奔,李霄等.树突状细胞和CD4+CD25+调节性T细胞在免疫耐受中的作用及关系.国际外科学杂志,2011,2,38(2):124-127