幽门螺杆菌致T细胞凋亡:Fas/FasL介导的T细胞无反应性

T cell anergy during Helicobacter pylori infection stems from the apoptosis mediated by Fas/FasL interaction

目的 评价幽门螺杆菌 (Hp)致T细胞死亡的方式和机制 ,探讨这种作用与Hp感染致宿主产生免疫耐受的关系。方法 应用AnnexinV染色流式细胞术检测Hp致T细胞死亡的方式 ;应用细胞毒实验 (JAM技术 )和FasIgG抗体、caspase 8抑制剂阻断实验评价T细胞凋亡与Fas FasL作用的关系 ,并通过流式细胞术直接检测Hp对T细胞FasL表达的上调作用及其与T细胞产生凋亡的时效关系。结果 AnnexinV染色和JAM技术证实Hp致T细胞死亡是以凋亡方式进行的。这种细胞凋亡能被抗Fas抗体和caspase 8抑制剂阻断 ,因而是Fas依赖的 ,TH2细胞较TH1样T细胞对这种作用更敏感。由于Hp能直接上调T细胞的FasL表达且其发生时间与凋亡出现时间吻合 ,证实Hp是通过调节T细胞之间Fas FasL相互作用而致其凋亡的。结论 Hp能通过调节Fas FasL作用而负调节T细胞的生长 ,这可能是Hp感染致宿主发生T细胞耐受的机制之一。

Objective Helicobacter pylori (H. pylori ) was capable of inhibiting T cell growth in vitro and this may explain the anergy of T cell to the infection in vivo . To elucidate this mechanism, T cell apoptosis was studied when exposed to H. pylori . Methods T cell apoptosis was identified by flow cytometry to detect the binding to Annexin V after the incubation with H. pylori . A co culture cytotoxicity assay (JAM) was used to evaluate the mechanism of T cell apoptosis. Fas ligand (FasL) expression on T cells was also detected by flowcytometry. Results Cell apoptosis in T cell lines (Jurkat and Cem C7) initiated after exposure to H. pylori as proven by Annexin V staining assay. The susceptibility of T H2 cell line Cem C7 to H. pylori was higher than that of non T H2 cell line. T cell apoptosis caused by H. pylori could be blocked by anti Fas blocking antibody and caspase 8 inhibitor. It suggested that the T cell apoptosis was mediated by Fas/FasL system. Direct detection of FasL expression indicated that H. pylori was capable of up regulating FasL expression on T cell and this happened coincidentally with the arising potential of T cell apoptosis. Conclusion Fas/FasL mediated apoptotic suicide or patricide of T cells, especially T H2 cells induced by H. pylori may explain the T cell anergy during the infection.