可诱导共刺激分子在白塞病免疫病理过程中的作用机制
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摘要
目的检测可诱导共刺激分子(inducible co-stimulator, ICOS)在BD患者外周血T细胞亚群的表达,探索其与BD疾病活动期和BD稳定期的关系,为进一步研究ICOS在BD免疫病理中的作用奠定基础;我们还检测了BD患者外周血INF-γ和IL-4的分泌水平,以便进一步了解BD患者外周血Th1/Th2以及Tc1/Tc2细胞的比例变化,探索BD患者体内的免疫状况。
方法采用流式细胞术检测华中科技大学同济医学院附属协和医院皮肤科门诊和住院BD活动期患者(n=22),BD稳定期(n=6)以及健康体检者(n=22)外周血T细胞亚群表面ICOS的表达水平以及INF-γ和IL-4的分泌水平,观察ICOS在不同T细胞亚群表达水平与疾病关系。
结果1)与正常人相比活动期及稳定期BD患者外周血CD4+T细胞百分比无统计学差异(P>0.05),而CD8+T细胞则存在显著差异(P<0.05),CD4/CD8比值也明显降低(P<0.05),CD4+CD28+和CD8+CD28+的百分率也明显下降(P<0.05); 2)与正常人相比活动期BD患者外周血CD4+T细胞和CD8+T细胞表达ICOS的水平显著升高(P<0.05),但稳定期患者与正常人之间无统计学差异(P>0.05),BD活动期CD28+ICOS+/CD4+、CD28-ICOS+/CD4+和CD28-ICOS+/CD8+与正常人相比显著升高(P<0.05),而BD稳定期CD28+ICOS+/CD4+、CD28-ICOS+/CD4+、CD28+ICOS+/CD8+及CD28-ICOS+/CD8+与正常人相比则无显著性差异(P>0.05); 3)BD患者活动期外周血细胞Th细胞和Tc细胞经过刺激后胞内合成IFN-γ的水平明显高于正常人水平(p < 0.05 ),稳定期患者Th细胞和Tc细胞体外合成IFN-γ的能力与正常人相比无明显差异(p>0.05),稳定期患者Th细胞和Tc细胞胞内合成IL-4的能力相对于正常人均无明显差异,但总体水平却略有上升趋势(p>0.05),而活动期患者Th细胞和Tc细胞胞内合成IL-4的能力相对于正常人均存在明显差异(p<0.05)。
结论BD患者外周血某些T细胞亚群存在ICOS的高表达,INF-γ和IL-4的分泌水平明显升高,并与疾病活动期存在一定程度相关,因此ICOS可能参与了BD的免疫病理过程。
Objective To investigate the express of inducible co-stimulator(ICOS)on peripheral blood T lymphocyte subsets in patients of Behcet’s disease( BD ) and to find out the relationship with disease-activity, disease-stage so as to pave the way for future studying the possibly immunologically pathological role of ICOS in BD. The levels of INF-γand IL-4 secreted were tested on peripheral blood in patients of BD, and to find out the ratio of Th1/Th2 and Tc1/Tc2 on peripheral blood in patients of BD as so to study immune condition in patients of BD.
Methods Peripheral blood samples were collected from 22 patients with BD, and 6 patients of disease-stage. Three-color flow cytometry was used to detect the levels of ICOS expression on peripheral blood T lymphocyte subsets, and INF-γand IL-4 secrete on peripheral blood in patients of BD. The results and relationship of disease were analyzed. Twenty-two healthy subjects were used as controls.
Results The first, compared with the healthy subjects the percentage of CD4+ T cells was no significant on peripheral blood of BD(p>0.05), but CD8+ T cells was significantly decreased(p<0.05),the ratio of CD4+/CD8+ was significantly decreased(p<0.05), the percentages of CD4+CD28+ and CD8+CD28+ T cells were significantly decreased(all p<0.05). The second, compared with the healthy subjects the levels of ICOS expression CD4+ and CD8+T cells on peripheral blood T lymphocyte subsets in patients of BD during disease-activity were significantly increased(all p<0.05), but in patients of BD during disease-stage were no significant(all p>0.05); The levels of ICOS expression on peripheral blood CD4+CD28+ and CD4+CD28- and CD8+CD28- in patients of BD during disease-activity were significantly increased (all P<0.05 ) , but ICOS expression on peripheral blood CD4+CD28+ and CD4+CD28- and CD8+CD28+ and CD8+CD28- in patients of BD during disease-stage were significant(all P>0.05). The thirty, compared with healthy subjects the levels of INF-γsecreted were significantly increased on peripheral blood Th and Tc cells in patients of BD during disease-activity(P<0.05), but the levels of INF-γsecreted were no significant on peripheral blood Th and Tc cells in patients of BD during disease-stage (P>0.05), the levels of IL-4 secreted were significantly increased on peripheral blood Th and Tc cells in patients of BD during disease-activity(P<0.05), but the levels of IL-4 secreted were no significant on peripheral blood Th and Tc cells in patients of BD during disease-stage( P>0.05 ).
Conclusion ICOS is aberrantly highly expressed on certain peripheral blood T lymphocyte subsets in patients with BD, there are significantly increased between the levels of INF-γand IL-4 secreted , which is related to disease-activity, thus ICOS may play a role in BD pathogenesis.
方法采用流式细胞术检测华中科技大学同济医学院附属协和医院皮肤科门诊和住院BD活动期患者(n=22),BD稳定期(n=6)以及健康体检者(n=22)外周血T细胞亚群表面ICOS的表达水平以及INF-γ和IL-4的分泌水平,观察ICOS在不同T细胞亚群表达水平与疾病关系。
结果1)与正常人相比活动期及稳定期BD患者外周血CD4+T细胞百分比无统计学差异(P>0.05),而CD8+T细胞则存在显著差异(P<0.05),CD4/CD8比值也明显降低(P<0.05),CD4+CD28+和CD8+CD28+的百分率也明显下降(P<0.05); 2)与正常人相比活动期BD患者外周血CD4+T细胞和CD8+T细胞表达ICOS的水平显著升高(P<0.05),但稳定期患者与正常人之间无统计学差异(P>0.05),BD活动期CD28+ICOS+/CD4+、CD28-ICOS+/CD4+和CD28-ICOS+/CD8+与正常人相比显著升高(P<0.05),而BD稳定期CD28+ICOS+/CD4+、CD28-ICOS+/CD4+、CD28+ICOS+/CD8+及CD28-ICOS+/CD8+与正常人相比则无显著性差异(P>0.05); 3)BD患者活动期外周血细胞Th细胞和Tc细胞经过刺激后胞内合成IFN-γ的水平明显高于正常人水平(p < 0.05 ),稳定期患者Th细胞和Tc细胞体外合成IFN-γ的能力与正常人相比无明显差异(p>0.05),稳定期患者Th细胞和Tc细胞胞内合成IL-4的能力相对于正常人均无明显差异,但总体水平却略有上升趋势(p>0.05),而活动期患者Th细胞和Tc细胞胞内合成IL-4的能力相对于正常人均存在明显差异(p<0.05)。
结论BD患者外周血某些T细胞亚群存在ICOS的高表达,INF-γ和IL-4的分泌水平明显升高,并与疾病活动期存在一定程度相关,因此ICOS可能参与了BD的免疫病理过程。
Objective To investigate the express of inducible co-stimulator(ICOS)on peripheral blood T lymphocyte subsets in patients of Behcet’s disease( BD ) and to find out the relationship with disease-activity, disease-stage so as to pave the way for future studying the possibly immunologically pathological role of ICOS in BD. The levels of INF-γand IL-4 secreted were tested on peripheral blood in patients of BD, and to find out the ratio of Th1/Th2 and Tc1/Tc2 on peripheral blood in patients of BD as so to study immune condition in patients of BD.
Methods Peripheral blood samples were collected from 22 patients with BD, and 6 patients of disease-stage. Three-color flow cytometry was used to detect the levels of ICOS expression on peripheral blood T lymphocyte subsets, and INF-γand IL-4 secrete on peripheral blood in patients of BD. The results and relationship of disease were analyzed. Twenty-two healthy subjects were used as controls.
Results The first, compared with the healthy subjects the percentage of CD4+ T cells was no significant on peripheral blood of BD(p>0.05), but CD8+ T cells was significantly decreased(p<0.05),the ratio of CD4+/CD8+ was significantly decreased(p<0.05), the percentages of CD4+CD28+ and CD8+CD28+ T cells were significantly decreased(all p<0.05). The second, compared with the healthy subjects the levels of ICOS expression CD4+ and CD8+T cells on peripheral blood T lymphocyte subsets in patients of BD during disease-activity were significantly increased(all p<0.05), but in patients of BD during disease-stage were no significant(all p>0.05); The levels of ICOS expression on peripheral blood CD4+CD28+ and CD4+CD28- and CD8+CD28- in patients of BD during disease-activity were significantly increased (all P<0.05 ) , but ICOS expression on peripheral blood CD4+CD28+ and CD4+CD28- and CD8+CD28+ and CD8+CD28- in patients of BD during disease-stage were significant(all P>0.05). The thirty, compared with healthy subjects the levels of INF-γsecreted were significantly increased on peripheral blood Th and Tc cells in patients of BD during disease-activity(P<0.05), but the levels of INF-γsecreted were no significant on peripheral blood Th and Tc cells in patients of BD during disease-stage (P>0.05), the levels of IL-4 secreted were significantly increased on peripheral blood Th and Tc cells in patients of BD during disease-activity(P<0.05), but the levels of IL-4 secreted were no significant on peripheral blood Th and Tc cells in patients of BD during disease-stage( P>0.05 ).
Conclusion ICOS is aberrantly highly expressed on certain peripheral blood T lymphocyte subsets in patients with BD, there are significantly increased between the levels of INF-γand IL-4 secreted , which is related to disease-activity, thus ICOS may play a role in BD pathogenesis.
引文
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