Dual role of HIV Tat in regulation of apoptosis in T cells.
Dual role of HIV Tat in regulation of apoptosis in T cells.
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DOI：
10.4049/jimmunol.158.2.1014
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发表时间：
1997-01
影响因子：
4.4
通讯作者：
T. McCloskey;M. Ott;Eugene Tribble;Shabbir A. Khan;S. Teichberg;M. Paul;S. Pahwa;E. Verdin;N. Chirmule;N. Chirmule;N. Chirmule
中科院分区：
文献类型：
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作者：
T. McCloskey;M. Ott;Eugene Tribble;Shabbir A. Khan;S. Teichberg;M. Paul;S. Pahwa;E. Verdin;N. Chirmule;N. Chirmule;N. Chirmule
细胞凋亡被认为是HIV-1感染者体内CD4+T细胞耗尽的主要机制之一。值得注意的是，HIV-1感染的细胞似乎受到了保护，不会发生凋亡，而旁观者的细胞在感染的人的淋巴结中表现出更多的凋亡。在这项工作中，我们提出了HIV-1的反式激活蛋白TAT在调节T细胞凋亡方面具有双重作用的证据。在外源TAT蛋白诱导未感染T细胞凋亡的同时，稳定表达TAT蛋白的T细胞克隆不受激活诱导的细胞凋亡的影响。外源性TAT可增强抗CD3单抗、抗Fas IgM单抗和肿瘤坏死因子-α诱导的T细胞凋亡。抗TAT单抗可阻断TAT诱导的细胞凋亡，但不影响抗Fas-IgM单抗诱导的细胞凋亡。用全长TAT基因(101个氨基酸)转染Jurkat T细胞克隆，或在含有空载体的对照细胞中分析内源性表达的TAT。与单独转染载体的细胞相比，Tat101转基因克隆对抗CD3诱导的细胞凋亡具有抵抗作用。此外，T细胞表面的CD4分子与gp160和抗gp160抗体相互作用后，Tat101细胞的凋亡率明显低于单独转染载体的细胞。综上所述，我们的结果表明，HIV-1Tat可以调节细胞凋亡，这可能参与了艾滋病的免疫发病机制。
Apoptosis has been suggested to be one of the major mechanisms of depletion of CD4+ T cells in HIV-1-infected individuals. Remarkably, HIV-1-infected cells appear protected from apoptosis, whereas bystander cells show increased apoptosis in lymph nodes of infected individuals. In this work, we present evidence that the trans-activating protein of HIV-1, Tat, has a dual role in regulation of apoptosis in T cells. While addition of exogenous Tat protein induced apoptosis in uninfected T cells, T cell clones stably expressing the Tat protein were protected from activation-induced apoptosis. The addition of exogenous Tat potentiated anti-CD3 mAb, anti-Fas IgM mAb, and TNF-alpha-induced apoptosis of T cells. Pretreatment of Tat with anti-Tat Ab abrogated Tat-induced apoptosis, but did not affect anti-Fas IgM Ab-induced apoptosis. Endogenously expressed Tat was analyzed in Jurkat T cell clones transfected with either full-length tat gene (101 amino acids), or in control cells containing an empty vector. The Tat101-transfected clones were resistant to anti-CD3-induced apoptosis, when compared with cells transfected with vector alone. Furthermore, cross-linking of CD4 molecules on T cells with gp160 and anti-gp160 Ab showed markedly decreased apoptosis in Tat101 cells compared with that induced in cells transfected with vector alone. Taken together, our results indicate that HIV-1 Tat can regulate apoptosis that may contribute to the immunopathogenesis of AIDS.