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

T cell apoptosis has been proposed as an Important contributorto the functional defects and depletion of T cells in HIV-lnfectedIndividuals. However, the mechanisms Involved in this apoptosishave not been elucidated. We recently showed that peripheralblood T cells from HIV-infected individuals are especially susceptibleto Fas antigen-induced apoptosis. In this study we examine therole of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR)and CD30, receptors known to be involved In T cell activation-inducedcell death (AICD), in the spontaneous and activation (anti-CD3)-lnducedapoptosis of peripheral blood T cells from asymptomatic HIV-infectedindividuals. We report here that spontaneous and activation-InducedT cell apoptosis cannot be inhibited by reagents that blockinteractions of Fas, CTLA-4, p55 and p75 TNFR and CD30 withtheir respective ligands. We also show that IL-12, IFN-, IL-4and IL-10 cannot modify spontaneous, activation- and anti-Fas-inducedapoptosis. Anti-Fas preferentially Induced CD4⁺ T cell apoptosiswhereas AICD induced apoptosis equally In CD4⁺ and CD8⁺ T cells.We conclude that T cell AICD In HIV infection Is not mediatedby Fas, thus Indicating that Fas-Induced and activation-InducedT cell apoptosis are independent mechanisms of apoptosis whichmay play different roles in the pathogenesls of HIV infection.