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CrmA expression in T lymphocytes of transgenic mice inhibits CD95 (Fas/APO‐1)‐transduced apoptosis, but does not cause lymphadenopathy or autoimmune disease.
Author(s) -
Smith K. G.,
Strasser A.,
Vaux D. L.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00901.x
Subject(s) - biology , fas receptor , apoptosis , transgene , disease , immunology , autoimmune disease , autoimmune lymphoproliferative syndrome , genetically modified mouse , programmed cell death , virology , microbiology and biotechnology , gene , antibody , genetics , pathology , medicine
The cysteine protease interleukin‐1beta converting enzyme (ICE) is implicated as an effector of apoptosis in mammalian cells. Proteolytic activity of ICE can be blocked in vitro by the cytokine response modifier A (crmA), a serpin‐like protease inhibitor encoded by cowpox virus. Here we show that CD2 enhancer‐driven expression of crmA in T lymphocytes of transgenic mice (CD2‐crmA mice) reduces CD95 (Fas/APO‐1)‐transduced apoptosis in vitro to the level seen in CD95‐deficient mutant lpr mice, but does not protect against gamma‐radiation or corticosteroid‐induced cell death. Unlike lpr mice, CD2‐crmA transgenic mice developed 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.