Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals

T call apoptosis has been proposed as an Important contributor to the functional defects and depletion of T cells In HIV-lnfected Individuals. However, the mechanisms Involved in this apoptosis have not been elucidated. We recently showed that peripheral blood T cells from HIVinfected individuals are especially susceptible to Fas antigen-induced apoptosis. In this study we examine the role of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR) and CD30, receptors known to be involved In T cell activation-induced cell death (AICD), in the spontaneous and activation (anti-CD3>-lnduced apoptosis of peripheral blood T cells from asymptomatic HIVinfected individuals. We report here that spontaneous and activation-Induced T cell apoptosis cannot be inhibited by reagents that block interactions of Fas, CTLA-4, p55 and p75 TNFR and CD30 with their respective ligands. We also show that IL-12, IFN-7, IL-4 and IL-10 cannot modify spontaneous, activation- and antl-Fas-induced apoptosis. Anti-Fas preferentially induced CD4+ T cell apoptosis whereas AICD induced apoptosis equally in CD4+ and CD8+ T cells. We conclude that T cell AICD In HIV infection Is not mediated by Fas, thus Indicating that Fas-Induced and activation-Induced T cell apoptosis are independent mechanisms of apoptosis which may play different roles in the pathogenesis of HIV infection.