Abstract
Antigen receptor engagement on T lymphocytes activates transcription factors important for stimulating cytokine gene expression. This is critical for clonal expansion of antigen-specific T cells and propagation of immune responses. Additionally, under some conditions antigen receptor stimulation initiates apoptosis of T lymphocytes through the induced expression of CD95 ligand and its receptor. Here we demonstrate that 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 sites within the CD95 ligand promoter, identified through DNase I footprinting, bind NFAT proteins from nuclear extracts of activated T cells. Although both sites appear important for optimal expression of CD95 ligand in activated T cells, mutational analysis suggests that the distal NFAT site plays a more significant role. Furthermore, these sites do not appear to be required for constitutive CD95 ligand expression in Sertoli cells.
Highlights
Adaptive immune responses require the activation of T lymphocytes through antigen-specific T cell receptor (TCR)1 stimulation
The significance of CD95 ligand expression in the process of activation-induced cell death has been highlighted by recent studies that demonstrate that blocking CD95/CD95 ligand interactions prevents apoptosis of TCR-stimulated lymphocytes [5, 7]
Relatively little is known about factors that control inducible expression of CD95 ligand in lymphocytes or constitutive expression in epithelial cells of the eye or Sertoli cells within the testes
Summary
Adaptive immune responses require the activation of T lymphocytes through antigen-specific T cell receptor (TCR)1 stimulation. Recent work from our laboratory [28] utilizing a reporter construct driven by elements of the CD95 ligand promoter suggests that NFAT may play an important role in regulating CD95 ligand expression in activated T cells.
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