Westendorp M O, Frank R, Ochsenbauer C, Stricker K, Dhein J, Walczak H, Debatin K M, Krammer P H
Tumorimmunology Program, German Cancer Research Centre, Heidelberg.
Nature. 1995 Jun 8;375(6531):497-500. doi: 10.1038/375497a0.
The depletion of CD4+ T cells in AIDS is correlated with high turnover of the human immunodeficiency virus HIV-1 and associated with apoptosis. The molecular mechanism of apoptosis in HIV infection, however, is largely unknown. T-cell apoptosis might be affected by viral proteins such as HIV-1 Tat and gp120 (refs 10, 11). T-cell-receptor (TCR)-induced apoptosis was recently shown to involve the CD95 (APO-1/Fas) receptor. We show here that HIV-1 Tat strongly sensitizes TCR- and CD4(gp120)-induced apoptosis by upregulation of CD95 ligand expression. Concentrations of Tat found to be effective in cultures of HIV-1-infected cells were also observed in sera from HIV-1-infected individuals. Taken together, our results indicate that HIV-1 Tat and gp120 accelerate CD95-mediated, activation-induced T-cell apoptosis, a mechanism that may contribute to CD4+ T-cell depletion in AIDS.
艾滋病中CD4+ T细胞的耗竭与人类免疫缺陷病毒HIV-1的高周转率相关，并与细胞凋亡有关。然而，HIV感染中细胞凋亡的分子机制在很大程度上尚不清楚。T细胞凋亡可能受病毒蛋白如HIV-1 Tat和gp120的影响（参考文献10、11）。最近研究表明，T细胞受体（TCR）诱导的细胞凋亡涉及CD95（APO-1/Fas）受体。我们在此表明，HIV-1 Tat通过上调CD95配体的表达，强烈地使TCR和CD4（gp120）诱导的细胞凋亡敏感化。在HIV-1感染细胞培养物中发现有效的Tat浓度，也在HIV-1感染个体的血清中观察到。综上所述，我们的结果表明，HIV-1 Tat和gp120加速CD95介导的、激活诱导的T细胞凋亡，这一机制可能导致艾滋病中CD4+ T细胞的耗竭。
