c-FLICE inhibitory protein expression inhibits T-cell activation.
Cellular FLICE-inhibitory protein (c-FLIP) inhibits death receptor-mediated apoptosis by specific interaction with FADD and procaspase-8, and may thus interfere with activation events mediated by FADD and caspase-8. Recent studies, however, suggest that c-FLIP also transmits activation signals. The role of c-FLIP on T-cell activation was examined here using several transgenic mice with variable c-FLIP expression. In all c-FLIP-transgenic mice, Fas-mediated apoptosis and in vitro activation-induced T-cell death were suppressed, and T-cell proliferation and IL-2 production were inhibited. c-FLIP transgene also promoted in vivo thymocyte death. Higher c-FLIP transgene expression was correlated with a more profound suppression of T-cell activation and a prominent disturbance in mature thymocyte development. There was no evidence of increased activation and proliferation in all c-FLIP-transgenic T cells examined. Instead, suppression of T-cell activation in c-FLIP-transgenic T cells could be a combinatory effect of FADD/caspase-8-dependent signals and c-FLIP-specific activities.
Tai
T-S
TS
Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan, ROC.
Fang
L-W
LW
Lai
M-Z
MZ
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000502:physiology*; D029681:Arabidopsis Proteins / Q000378:metabolism*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002999:Clone Cells; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D029681:Arabidopsis Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C506387:Cflar protein, mouse; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; C505530:CASP8 protein, human; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases