Peptide epitope induced apoptosis of human cytotoxic T lymphocytes. Implications for peripheral T cell deletion and peptide vaccination

Abstract

Cloned CTL can be induced to undergo apoptosis with cognate peptide epitopes. This phenomenon has been attributed to self recognition and self destruction of individual, isolated CTL and/or Ag-induced cell death. It has been claimed that these mechanism are responsible for extrathymic elimination of primed CTL. In our study the contribution of all known effector mechanisms (single cell self killing, CTL-CTL killing, backward killing, bystander killing, Ag-induced cell death, and veto) to peptide epitope-induced destruction of CTL was evaluated. CTL-CTL killing was found to be the dominant mechanism, with a significant contribution from bystander killing. CTL were as susceptible to peptide-mediated lysis as conventional target cells. CTL, which were actively killing target cells, were not refractory to the lytic mechanisms of other CTL but paradoxically, avoid destruction by their own lytic mediators when delivering the lethal hit. These data imply that mature primed CTL are not deleted in the periphery as a direct result of the lysis of target cells, although, under certain circumstances peripheral CTL-CTL killing may be envisaged when cognate peptide is used for vaccination.