The Fas death pathway controls coordinated expansions of type 1 CD8 and type 2 CD4 T cells in Trypanosoma cruzi infection
The Fas death pathway controls coordinated expansions of type 1 CD8 and type 2 CD4 T cells in Trypanosoma cruzi infection
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DOI：
10.1189/jlb.1006643
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Lopes, Marcela F.
中科院分区：
文献类型：
--
作者：
Guillermo, Landi V. Costilla;Silva, Elisabeth M.;Lopes, Marcela F.
我们研究了Fas配体（Fast）/Fas死亡途径对克氏锥虫感染中T细胞凋亡和细胞因子产生的作用。抗FasL，而不是抗TNF-α或抗TRAIL，阻断活化诱导的CD 8 T细胞的细胞死亡，并增加来自T细胞的CD 4 T细胞分泌IL-10和IL-4。克氏病毒感染的小鼠CD 4和CD 8 T细胞在T.克氏感染然而，Fas表达在CD 8 T细胞中较早增加，并且与CD 4 T细胞相比，更高比例的CD 8 T细胞被激活并表达IFN-γ。感染小鼠注射抗FasL抗体可减少寄生虫血症和CD 8 T细胞凋亡，并增加从脾脏和腹膜回收的CD 8/CD 4 T细胞的比例。FasL阻断增加了活化T细胞的数量，增强了NO的产生，并减少了腹腔巨噬细胞中的寄生虫负荷。注射抗FasL抗体可增加T. cruzi抗原的表达，而且在急性感染的晚期阶段加剧了2型细胞因子IL-10和IL-4的产生。这些结果表明，FasL/Fas死亡途径调节T细胞中1型CD 8和2型CD 4 T细胞的凋亡和协调的细胞因子应答。克氏感染
We investigated the role of the Fas ligand (Fast)/Fas death pathway on apoptosis and cytokine production by T cells in Trypanosoma cruzi infection. Anti-FasL, but not anti-TNF-alpha or anti-TRAIL, blocked activation-induced cell death of CD8 T cells and increased secretion of IL-10 and IL-4 by CD4 T cells from T. cruzi-infected mice. CD4 and CD8 T cells up-regulated Fas/FasL expression during T. cruzi infection. However, Fas expression increased earlier in CD8 T cells, and a higher proportion of CD8 T cells was activated and expressed IFN-gamma compared with CD4 T cells. Injection of anti-FasL in infected mice reduced parasitemia and CD8 T cell apoptosis and increased the ratio of CD8:CD4 T cells recovered from spleen and peritoneum. FasL blockade increased the number of activated T cells, enhanced NO production, and reduced parasite loads in peritoneal macrophages. Injection of anti-FasL increased IFN-gamma secretion by splenocytes responding to T. cruzi antigens but also exacerbated production of type 2 cytokines IL-10 and IL-4 at a late stage of acute infection. These results indicate that the FasL/Fas death pathway regulates apoptosis and coordinated cytokine responses by type 1 CD8 and type 2 CD4 T cells in T. cruzi infection.