SENSITIZATION OF T-CELLS TO CD95-MEDIATED APOPTOSIS BY HIV-1 TAT AND GP120

THE depletion of CD4(+) T cells in AIDS is correlated with high turnov er of the human immunodeficiency virus HIV-1(1,2) acid associated with apoptosis(3-5). The molecular mechanism of apoptosis in HIV infection , however, is largely unknown, T-cell apoptosis might be affected by v iral proteins such as HIV-1 Tat(6-9) and gp120 (refs 10, 11). T-cell-r eceptor (TCR)-induced apoptosis was recently shown to involve the CD95 (APO-1/Fas) receptor(12). We show here that HIV-1 Tat strongly sensit izes TCR- and CD4(gp120)-induced apoptosis by upregulation of CD95 lig and expression. Concentrations of Tat found to be effective in culture s of HIV-1-infected cells were also observed in sera from HIV-1-infect ed individuals. Taken together, our results indicate that HIV-1 Tat an d gp120 accelerate CD95-mediated, activation-induced T-cell apoptosis, a mechanism that may contribute to CD4(+) T-cell depletion(5,13,14) i n AIDS.