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

T cell apoptosis has been proposed as an important contributor to the functional defects and depletion of T cells in HIV-infected individuals, However, the mechanisms involved in this apoptosis have not been elucidated, We recently showed that peripheral blood T cells from HIV-infected 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)-induced apoptosis of peripheral blood T cells from asymptomatic HIV-infected 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-gamma, IL-4 and IL-10 cannot modify spontaneous, activation- and anti-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.