Regulation of CD95 (FAS) ligand expression in activated T cells and immune privileged tissues

Academic Article

Abstract

  • Following stimulation through the antigen receptor, T cells receive signals to produce cytokines and subsequently to proliferate. However, to maintain homeostasis, activated T cells also increase expression of the effectors of apoptosis, CD95 and CD95 ligand. Interestingly, constitutively expressed CD95 ligand on epithelial cells of the eye and Sertoli cells within the testes also participates in the maintenance of "immune privilege" in these tissues. However, despite the importance of CD95 ligand in these processes, little is known about what controls its inducible expression in T cells and constitutive expression in Sertoli cells. Mobility shift studies and reporter assays aimed at identifying transcription factors which regulate CD95 ligand expression demonstrate that two NFAT binding sites and a CACCC-based response element are required for optimal expression in activated T cells. Interestingly, these sites are not required for constitutive CD95 ligand promoter activity in Sertoli cells. Finally, studies of CD95 ligand luciferase reporter transgenic mice confirm the constitutive expression in immune privileged tissues and inducible expression in isolated T cell populations. Further examination of the CD95 ligand promoter m cell lines as well as analysis of the transgenic mice should provide further insight into what controls CD95 ligand expression in activated T cells and cells of immune privileged tissues.
  • Author List

  • Latinis KM; Norian LA; Koretzky GA
  • Volume

  • 12
  • Issue

  • 5