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-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.
The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
K G
KG
Smith
A
A
Strasser
D L
DL
Vaux
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001323:Autoantibodies / Q000097:blood; D018801:CD2 Antigens / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005720:Gamma Rays; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D015843:Serpins / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000737:chemistry; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D018800:Thy-1 Antigens / Q000032:analysis; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology / Q000528:radiation effects; D014764:Viral Proteins; D019014:fas Receptor / Q000032:analysis / Q000502:physiology*
D001323:Autoantibodies; D018801:CD2 Antigens; D005938:Glucocorticoids; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015843:Serpins; D018800:Thy-1 Antigens; D014764:Viral Proteins; D019014:fas Receptor; D003907:Dexamethasone; C074641:interleukin-1beta-converting enzyme inhibitor