环孢素A对小鼠Th17细胞分化的影响  

The effects of CsA on the differentiation of Th17 cells

作　　者：王俨[1] 吴长有[1] 

机构地区：[1]中山大学中山医学院免疫学教研室热带传染病教育部重点实验室,广州510080

出　　处：《中国免疫学杂志》2008年第8期675-678,684,共5页Chinese Journal of Immunology

基　　金：国家973项目(No.2007CB512404);广东省自然科学基金团队项目(05200176)资助

摘　　要：目的:观察在抗CD3单克隆抗体(mAb)+rIL-23刺激的条件下,环孢素A(CsA)对Th17细胞分化的影响。方法:小鼠脾淋巴细胞分别使用抗CD3 mAb、抗CD3 mAb+rIL-23及抗CD3 mAb+rIL-23+不同浓度的CsA刺激后,用ELISA检测IL-17和IFN-γ的水平,并用流式细胞仪在单个细胞水平上检测产生IL-17的T细胞亚群。结果:单独抗CD3 mAb能诱导少量的IL-17产生,加入IL-23后呈剂量依赖的方式明显增加IL-17的产生。CsA对抗CD3 mAb+rIL-23诱导的Th17细胞分化呈剂量依赖性的抑制作用。CsA不仅抑制早期Th17的分化,当细胞激活48小时后,CsA对Th17细胞的分化仍有抑制作用。CsA除了抑制Th17细胞分化外,对IFN-γ和IL-2的产生也有抑制作用。此外,T细胞亚群分析的结果表明IL-17主要由CD4+T细胞产生,而CD8+T细胞几乎不产生IL-17。结论:CsA可以抑制Th17细胞的分化,进一步阐明了CsA免疫抑制及抗炎作用的机制,为临床上应用CsA提供科学理论和实验依据。Objective： To examine the effect of cyclosporine A （CsA） on the differentiation of Th17 ceils from splenocytes after stimulation with anti-CD3 mAb ＋ IL-23. Methods： Total splenocytes were cultured with anti-CD3 mAb alone or anti-CD3 mAb plus IL-23 in the presence or absence of different concentrations of CsA. After stimtdation,produetion of IL-17 and IFN-γ was assayed by ELISA.The subsets of IL- 17-producting T cells were examined at single-cell level by flow cytometry. Results： The splenocytes stimulated with anti-CD3 mAb alone could induce low level of IL- 17 production and addition of IL-23 could promote high level of IL-17 in a dose-dependent manner. CsA inhibited the differentiantion of Th17 cells from splenocytes stimulated with anti-CD3 mAb ＋ IL-23 in a dose-dependent manner. Kinetic studies indicated that CsA also inhibited the differentiantion of Th17 ceils from activated T cells stimulated by anti-CD3 mAb＋ IL-23 for 48 hours. In addition,CsA inhibited production of IFN-γ and IL-2. The analysis of subsets of T cells demonstrated that CD4＋ T cells but not CD8＋ T cells produced IL-17. Conclusion： CsA can inhibit Th17 cell differentiation. This observation shed a new light on the potential mechanisms for the immunosuppressive and anti-inflammatory functions of CsA and provideds a theoretical and experimental foundation for clinical application.

关 键 词：环胞素A TH17 IFN-Γ 

分 类 号：R392[医药卫生—免疫学]