CNRS UMR5239, Université de Lyon, Oncovirologie et Biothérapies, Centre Léon Bérard, 69008 Lyon, France.
Virology. 2010 Nov 25;407(2):341-51. doi: 10.1016/j.virol.2010.07.023. Epub 2010 Sep 22.
Here we investigate the mechanisms by which HTLV-1 infection prevents the cell death of CD8(+) T cells in vivo. We show that upon natural infection, cloned CD8(+) but not CD4(+) cells from patients without malignancy become resistant to Fas-mediated cell death and acquire an antiapoptotic transcriptome that includes the overexpression of cIAP-2 and c-FLIP(L). CD8(+) lymphocyte-restricted cIAP-2 overexpression correlates with resistance to Fas-mediated apoptosis and depends on tax expression via NF-KappaB. In contrast, in the same CD8(+) cells, the HTLV-1-dependent overexpression of c-FLIP(L) does not correlate with resistance to Fas-mediated cell death nor with tax expression. In the present model, infected CD8(+) clones are the only cell subtype in which cIAP-2 expression correlates with resistance to cell death. These results support a role for Tax-dependent cIAP-2 expression in preventing the death of naturally infected CD8(+) cells and thereby in their clonal expansion in vivo.
在这里，我们研究了 HTLV-1 感染防止体内 CD8(+) T 细胞死亡的机制。我们表明，在自然感染中，来自没有恶性肿瘤的患者的克隆 CD8(+)但不是 CD4(+)细胞对 Fas 介导的细胞死亡具有抗性，并获得了包括 cIAP-2 和 c-FLIP(L)过度表达的抗凋亡转录组。CD8(+)淋巴细胞受限的 cIAP-2 过度表达与 Fas 介导的细胞凋亡的抗性相关，并且依赖于通过 NF-KappaB 的 tax 表达。相比之下，在相同的 CD8(+)细胞中，HTLV-1 依赖性 c-FLIP(L)的过度表达与 Fas 介导的细胞死亡的抗性或 tax 表达无关。在本模型中，感染的 CD8(+)克隆是唯一与细胞死亡抗性相关的 cIAP-2 表达的细胞亚型。这些结果支持 Tax 依赖性 cIAP-2 表达在防止自然感染的 CD8(+)细胞死亡以及随后在体内的克隆扩增中的作用。
