CD4 regulates susceptibility to Fas ligand- and tumor necrosis factor-mediated apoptosis.
CD4 regulates susceptibility to Fas ligand- and tumor necrosis factor-mediated apoptosis.
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DOI：
10.1084/jem.187.5.711
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发表时间：
1998-03-02
期刊：
影响因子：
--
通讯作者：
Paya CV
中科院分区：
文献类型：
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作者：
Algeciras A;Dockrell DH;Lynch DH;Paya CV
目前对CD4功能的了解仅限于其作为TCR启动信号传导中必要的辅助受体的作用。我们已经研究了CD4是否调节额外的T细胞功能。使用人初级静息CD4+ T细胞，我们证明了CD4活化足以诱导淋巴细胞死亡。CD4交联后，CD4+ T细胞立即对TNF或FasL介导的细胞凋亡敏感。这与在相同群体内的FasL的伴随诱导一起导致显著的体外CD4+ T细胞死亡。由TNF或FasL介导的CD4依赖性诱导对细胞凋亡的易感性是蛋白质合成无关的，但依赖于磷酸化。在CD4活化后，PKC调节FasL介导的凋亡易感性，但不诱导TNF依赖性凋亡易感性。此外，CD3和CD4活化之间的显着差异，观察到的动力学诱导的CD4+ T细胞对FasL和TNF介导的细胞凋亡的易感性。总之，这些结果提供了一个模型，其中研究的分子机制调节淋巴细胞存活后，CD4活化，并强调在控制淋巴细胞凋亡的生理条件下，或在疾病状态，如HIV感染的CD4的潜在作用。
The current knowledge of CD4 function is limited to its role as a necessary coreceptor in TCR-initiated signaling. We have investigated whether CD4 regulates additional T cell functions. Using human primary resting CD4+ T cells, we demonstrate that CD4 activation is sufficient to induce lymphocyte death. Immediately after CD4 cross-linking, CD4+ T cells are rendered susceptible to apoptosis mediated by TNF or FasL. This, together with the concomitant induction of FasL within the same population, results in significant CD4+ T cell death in vitro. The CD4-dependent induction of susceptibility to apoptosis that is mediated by TNF or FasL is protein synthesis independent but phosphorylation dependent. After CD4 activation, PKC regulates susceptibility to apoptosis mediated by FasL but not the induction of susceptibility to TNF-dependent apoptosis. Moreover, significant differences between CD3 and CD4 activation were observed with regards to the kinetics of induction of CD4+ T cell susceptibility to FasL- and TNF-mediated apoptosis. Altogether, these results provide a model with which to study the molecular mechanisms regulating lymphocyte survival after CD4 activation, and highlight the potential role of CD4 in controlling lymphocyte apoptosis under physiological conditions or in disease states such as HIV infection.