Koga Y
Department of Infectious Diseases, Tokai University School of Medicine.
Nihon Rinsho. 1996 Jul;54(7):1842-7.
Evidence is accumulating that apoptotic pathways account for the depletion of CD4 T cells in HIV-1 infected individuals. These pathways may be mediated, either directly by a virus infection or indirectly, through the priming of uninfected cells to apoptosis, when triggered by different agents. The participation of apoptosis in the cytopathic effect of CD4 T cells infected with HIV, in vitro, has already been shown. In our study using human CD4 cell clones expressing gp160 of HIV-1 under the control of inducible promoter, cell killing due to apoptosis was induced in the cells when gp160 was synthesized and a complex formed with gp160 in the cell. Non-infected CD4 T cells present in the vicinity of an infected cell may be killed through several mechanisms that involve gp120-CD4 interactions. Gp120 shed from infected cells can interact with CD4 on non-infected cells. Cross-linking of CD4 by such gp120 or by further binding of anti-gp120 antibody to gp120 may prime CD4 T cells for apoptosis following antigen-driven activation.
越来越多的证据表明，凋亡途径是导致HIV-1感染者CD4 T细胞耗竭的原因。这些途径可能直接由病毒感染介导，也可能间接介导，即在不同因子触发时，通过使未感染细胞启动凋亡来实现。体外实验已表明凋亡参与了HIV感染的CD4 T细胞的细胞病变效应。在我们的研究中，使用在诱导型启动子控制下表达HIV-1 gp160的人CD4细胞克隆，当gp160合成并在细胞内与gp160形成复合物时，细胞因凋亡而被杀伤。感染细胞附近存在的未感染CD4 T细胞可能通过几种涉及gp120-CD4相互作用的机制被杀死。从感染细胞中脱落的gp120可与未感染细胞上的CD4相互作用。这种gp120或抗gp120抗体与gp120的进一步结合对CD4的交联，可能会使CD4 T细胞在抗原驱动的激活后启动凋亡。
