CRMA EXPRESSION IN T-LYMPHOCYTES OF TRANSGENIC MICE INHIBITS CD95 (FAS APO-1)-TRANSDUCED APOPTOSIS, BUT DOES NOT CAUSE LYMPHADENOPATHY OR AUTOIMMUNE-DISEASE/

The cysteine protease interleukin-1 beta converting enzyme (ICE) is im plicated as an effector of apoptosis in mammalian cells. Proteolytic a ctivity of ICE can be blocked in vitro by the cgtokine response modifi er A (crmA), a serpin-like protease inhibitor encoded by cow-pox virus . Here we show that CD2 enhancer-driven expression of crmA in T lympho cytes of transgenic mice (CD2-crmA mice) reduces CD95 (Fas/APO-1)-tran sduced apoptosis in vitro to the level seen in CD95-deficient mutant l pr mice, but does not protect against gamma-radiation or corticosteroi d-induced cell death. Unlike lpr mice, CD2-crmA transgenic mice develo ped neither T cell hyperplasia nor serum autoantibodies. These results provide evidence that the phenotype of lpr mice is not simply due to failure of CD95 to trigger T cell apoptosis mediated by ICE.