Cutting edge: The class II transactivator prevents activation-induced celldeath by inhibiting Fas ligand gene expression

Fas:Fas ligand pathway is critical in regulating immune homeostasis by elim inating activated T cells that proliferated in response to an infection. He re, ne show that the MHC class II transactivator (CIITA) can suppress this pathway by inhibiting transcription of the Fas ligand gene. CIITA can effec tively repress transcription from the Fas ligand promoter in both T cell li nes as well as primary cells. The repression appears to be at least partly due to interference of NFAT-mediated induction of Fos ligand gene transcrip tion. T cells that express CIITA constitutively do not up-regulate Fas liga nd on the cell surface after activation ria the TCR. Consequently, these ce lls lack the ability to undergo activation-induced cell death, and to kill Fas-bearing target cells.