Resistance of short term activated T cells to CD95-mediated apoptosis correlates with de novo protein synthesis of c-FLIPshort
Resistance of short term activated T cells to CD95-mediated apoptosis correlates with de novo protein synthesis of c-FLIPshort
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DOI：
10.4049/jimmunol.172.4.2194
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发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Kirchhoff, S
中科院分区：
文献类型：
--
作者：
Schmitz, I;Weyd, H;Kirchhoff, S
在免疫应答的早期阶段，T细胞被激活并获得效应子功能。尽管这些短期活化的T细胞对CD 95介导的细胞凋亡具有抗性，但长期培养的活化的T细胞容易敏感，导致活化诱导的细胞死亡和免疫应答的终止。翻译抑制剂放线菌酮部分克服了短期活化的原代人T细胞的凋亡抗性。使用这个模型，我们在这项研究中表明，敏化T细胞凋亡发生在线粒体上游。在致敏T细胞中，死亡诱导信号复合物的形成和Bcl-2蛋白的表达都没有改变。虽然caspase-8抑制剂c-FLIPlong在致敏T细胞中仅轻微下调，但c-FLIPshort几乎检测不到。这与caspase-8激活和凋亡相关。这些数据表明，c-FLIP短，而不是c-FLIP长，赋予T细胞在免疫应答的背景下CD 95介导的细胞凋亡的抗性。
In the early phase of an immune response, T cells are activated and acquire effector functions. Whereas these short term activated T cells are resistant to CD95-mediated apoptosis, activated T cells in prolonged culture are readily sensitive, leading to activation-induced cell death and termination of the immune response. The translation inhibitor, cycloheximide, partially overcomes the apoptosis resistance of short term activated primary human T cells. Using this model we show in this study that sensitization of T cells to apoptosis occurs upstream of mitochondria. Neither death-inducing signaling complex formation nor expression of Bcl-2 proteins is altered in sensitized T cells. Although the caspase-8 inhibitor c-FLIPlong was only slightly down-regulated in sensitized T cells, c-FLIPshort became almost undetectable. This correlated with caspase-8 activation and apoptosis. These data suggest that c-FLIPshort, rather than c-FLIPlong, confers resistance of T cells to CD95-mediated apoptosis in the context of immune responses.