HIV-1 directly kills CD4+ T cells by a Fas-independent mechanism.
HIV-1 directly kills CD4+ T cells by a Fas-independent mechanism.
复制标题
DOI：
10.1084/jem.187.7.1113
复制
发表时间：
1998-04-06
期刊：
影响因子：
--
通讯作者：
Baltimore D
中科院分区：
文献类型：
--
作者：
Gandhi RT;Chen BK;Straus SE;Dale JK;Lenardo MJ;Baltimore D
HIV-1诱导CD 4 + T细胞死亡的机制尚不清楚。一个根本的问题是HIV-1是否主要诱导直接杀死受感染的细胞或间接导致未感染的旁观者细胞死亡。这个问题进行了研究，使用报告病毒系统，其中感染的细胞与细胞表面蛋白胎盘碱性磷酸酶（PLAP）标记。外周血单核细胞（PBMC）和T细胞系的HIV-PLAP感染导致CD 4 + T细胞的快速消耗和细胞凋亡的诱导。在体外，HIV诱导的T细胞死亡绝大多数涉及感染细胞的直接损失，而不是对未感染的旁观者细胞的间接影响。由于其在HIV诱导的细胞死亡中的作用，我们还研究了Fas（CD 95/Apo 1）途径在HIV-1杀死T细胞中的作用。感染的PBMC或CEM细胞相对于未感染的细胞显示表面Fas没有增加。此外，HIV-1在完全阻断Fas介导的细胞凋亡的半胱天冬酶抑制剂存在下杀死CEM和Jurkat T细胞。HIV-1还消耗来自具有遗传缺陷的Fas途径的患者的PBMC中的CD 4 + T细胞。这些结果表明，HIV-1诱导感染细胞的直接凋亡，并通过Fas非依赖性机制杀死T细胞。
The mechanism by which HIV-1 induces CD4+ T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected bystander cells. This question was studied using a reporter virus system in which infected cells are marked with the cell surface protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid depletion of CD4+ T cells and induction of apoptosis. The great majority of HIV-induced T cell death in vitro involves direct loss of infected cells rather than indirect effects on uninfected bystander cells. Because of its proposed role in HIV-induced cell death, we also examined the Fas (CD95/Apo1) pathway in killing of T cells by HIV-1. Infected PBMCs or CEM cells display no increase in surface Fas relative to uninfected cells. In addition, HIV-1 kills CEM and Jurkat T cells in the presence of a caspase inhibitor that completely blocks Fas-mediated apoptosis. HIV-1 also depletes CD4+ T cells in PBMCs from patients who have a genetically defective Fas pathway. These results suggest that HIV-1 induces direct apoptosis of infected cells and kills T cells by a Fas-independent mechanism.