HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death
HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death
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DOI：
10.4049/jimmunol.174.9.5249
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Krammer, PH
中科院分区：
文献类型：
--
作者：
Gülow, K;Kaminski, M;Krammer, PH
免疫反应的终止需要通过激活诱导细胞死亡 (AICD) 消除激活的 T 淋巴细胞。在 AICD 中，CD95 (Apo-1/Fas) 配体 (L) 触发 CD95 阳性活化 T 淋巴细胞凋亡。在艾滋病患者中，AICD 被强烈增强和加速。我们和其他人之前已经证明，HIV-1 转录反式激活剂 (HIV-1 Tat) 使 T 细胞对 CD95 介导的细胞凋亡敏感，并通过影响细胞氧化还原平衡来上调 CD95L 表达。在这项研究中，我们证明过氧化氢 (11202) 在 TCR 信号传导中充当重要的第二信使。 11,02 信号与同时流入细胞质的钙 (Ca2(+)) 构成了诱导 CD95L 表达的最低要求。单独使用任何一个信号都是不够的。我们进一步表明 HIV-1 Tat 干扰 TCR 信号传导并诱导 H2O2 信号。 HIV-1 Tat 产生的 H2O2 与 CD4 依赖性钙流入结合，导致大量 T 细胞凋亡。因此，我们的数据为 AIDS 进展过程中 CD4(+) T 淋巴细胞的耗竭提供了解释。
Termination of an immune response requires elimination of activated T lymphocytes by activation-induced cell death (AICD). In AICD, CD95 (Apo-1/Fas) ligand (L) triggers apoptosis of CD95-positive activated T lymphocytes. In AIDS patients, AICD is strongly enhanced and accelerated. We and others have previously shown that HIV-1 trans-activator of transcription (HIV-1 Tat) sensitizes T cells toward CD95-mediated apoptosis and up-regulates CD95L expression by affecting the cellular redox balance. In this study, we show that it is hydrogen peroxide (11202) that functions as an essential second messenger in TCR signaling. The 11,02 signal combined with simultaneous calcium (Ca2(+)) influx into the cytosol constitutes the minimal requirement for induction of CD95L expression. Either signal alone is insufficient. We further show that HIV-1 Tat interferes with TCR signaling and induces a H2O2 signal. H2O2 generated by HIV-1 Tat combines with CD4-dependent calcium influx and causes massive T cell apoptosis. Thus, our data provide an explanation for CD4(+) T lymphocyte depletion during progression of AIDS.