Caspases in T-cell receptor-induced thymocyte apoptosis

Apoptosis eliminates inappropriate or autoreactive T lymphocytes during thy mic development. Intracellular mediators involved in T-cell receptor (TCR)- mediated apoptosis in developing thymocytes during negative selection are t herefore of great interest. Caspases, cysteine proteases that mediate matur e T-cell apoptosis, have been implicated in thymocyte cell death, but their regulation is not understood. We examined caspase activities in distinct t hymocyte subpopulations that represent different stages of T-cell developme nt. We found caspase activity in CD4(+)CD8(+) double positive (DP) thymocyt es, where selection involving apoptosis occurs. Earlier and later thymocyte stages exhibited no caspase activity. Only certain caspases, such as caspa se-3 and caspase-8-like proteases, but not caspase-1, are active in DP thym ocytes in vivo and can be activated when DP thymocytes are induced to under go apoptosis in vitro by TCR-crosslinking. Thus, specific caspases appear t o be developmentally regulated in thymocytes.