Different programs of activation-induced cell death are triggered in mature activated CTL by immunogenic and partially agonistic peptide ligands

Activation-induced cell death (AICD) of mature T cells plays an important r ole in the control of immune homeostasis and peripheral tolerance. TNFRs an d Pas have been implicated in the induction of AICD. However, these molecul es were shown to be dispensable, at least in some experimental systems, for downsizing of Ag-induced T cell expansions and development of tolerance in vivo. The conditions of T cell activation leading to T cell deletion in a death receptor-independent manner are not well characterized. Here we show that human CTLs die through a death receptor-independent apoptotic program upon triggering with a partially agonistic peptide ligand. This apoptotic p rocess exhibits some features of T cell death due to lymphokine deprivation and is blocked by exogenous IL-2. Our data demonstrate that engagement of TCR by MHC-peptide complexes can trigger diverse apoptotic programs of AICD and that the choice between these programs is determined by the agonistic potency of MHC-peptide ligand.