2 NFAT TRANSCRIPTION FACTOR-BINDING SITES PARTICIPATE IN THE REGULATION OF CD95 (FAS) LIGAND EXPRESSION IN ACTIVATED HUMAN T-CELLS

Antigen receptor engagement on T lymphocytes activates transcription f actors important for stimulating cytokine gene expression, This is cri tical for clonal expansion of antigen-specific T cells and propagation of immune responses. Additionally, under some conditions antigen rece ptor stimulation initiates apoptosis of T lymphocytes through the indu ced expression of CD95 ligand and its receptor. Here we demonstrate th at the transcription factor, NFAT, which is critical for the inducible expression of many cytokine genes, also plays a critical role in the regulation of T cell receptor-mediated CD95 ligand expression, Two sit es within the CD95 ligand promoter, identified through DNase I footpri nting, bind NFAT proteins from nuclear extracts of activated T cells. Although both sites appear important for optimal expression of CD95 li gand in activated T cells, mutational analysis suggests that the dista l NFAT site plays a more significant role. Furthermore, these sites do not appear to be required for constitutive CD95 ligand expression in Sertoli cells.