Cutting edge: the class II transactivator prevents activation-induced cell death by inhibiting Fas ligand gene expression.
The Fas:Fas ligand pathway is critical in regulating immune homeostasis by eliminating activated T cells that proliferated in response to an infection. Here, we show that the MHC class II transactivator (CIITA) can suppress this pathway by inhibiting transcription of the Fas ligand gene. CIITA can effectively repress transcription from the Fas ligand promoter in both T cell lines as well as primary cells. The repression appears to be at least partly due to interference of NFAT-mediated induction of Fas ligand gene transcription. T cells that express CIITA constitutively do not up-regulate Fas ligand on the cell surface after activation via the TCR. Consequently, these cells lack the ability to undergo activation-induced cell death, and to kill Fas-bearing target cells.
Gourley
T S
TS
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Chang
C H
CH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015759:Ionomycin / Q000633:toxicity; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007166:Immunosuppressive Agents; D008024:Ligands; C083728:MHC class II transactivator protein; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D019014:fas Receptor; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate