Antigen-dependent release of IFN-gamma by cytotoxic T cells up-regulates Fas on target cells and facilitates exocytosis-independent specific target cell lysis

J Immunol. 2002 Jul 1;169(1):145-50. doi: 10.4049/jimmunol.169.1.145.

Abstract

Effector cytolytic T (Tc) lymphocytes, deficient in the exocytosis-mediated pathway of target cell lysis, induce Fas on target cells and, in turn, delayed cell death and apoptosis via the Fas ligand-Fas interaction. The induction of Fas can be blocked by anti- IFN-gamma Abs. This Fas up-regulation on initially Fas-negative target cells is not mediated by TCR-MHC/peptide signaling per se, but by secreted IFN-gamma from Tc cells after Ag engagement. The Fas up-regulation by Tc cells can be mimicked by treatment of target cells with rIFN-gamma. Tc cells from IFN-gamma knockout mice do not induce Fas expression on target cells. Tc cell-mediated Fas expression on third party, bystander, target cells does not enhance their susceptibility to lysis by these nominal effector cells. The results are discussed as to the possible relevance of the phenomenon in efficiency and regulation of the Tc cell response to infections by viruses.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Bystander Effect / immunology
  • Chromium Radioisotopes / metabolism
  • Cytotoxicity Tests, Immunologic / methods
  • Cytotoxicity, Immunologic* / genetics
  • DNA / antagonists & inhibitors
  • DNA Fragmentation / genetics
  • DNA Fragmentation / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Exocytosis / genetics
  • Exocytosis / immunology*
  • H-2 Antigens / physiology*
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Interferon-gamma / pharmacology
  • L Cells
  • Leukemia L1210
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Recombinant Proteins / pharmacology
  • Serine Endopeptidases / deficiency
  • Serine Endopeptidases / genetics
  • Solubility
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Up-Regulation / genetics
  • Up-Regulation / immunology*
  • fas Receptor / biosynthesis*
  • fas Receptor / physiology

Substances

  • Antibodies, Monoclonal
  • Chromium Radioisotopes
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2K(K) antigen
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Recombinant Proteins
  • fas Receptor
  • Perforin
  • Interferon-gamma
  • DNA
  • Serine Endopeptidases