Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

Front Immunol. 2021 Mar 24:12:635862. doi: 10.3389/fimmu.2021.635862. eCollection 2021.

Abstract

Activation of self-reactive CD8+ T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of Fas and Fasl causes the accumulation of double-negative (DN; CD3+ TCR-αβ+ CD4- CD8-) T cells that have been proposed to derive from CD8+ cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and FasL induction by different stimuli and analyzed the effects of Fas/FasL deficiency during a protective immune response and after exposure to self-antigens. Our data describes how Fas and FasL upregulation differs depending on the setting of CD8 T cell activation and demonstrates that Fas/FasL signaling maintains CD8 expression during repetitive antigen stimulation and following self-antigen encounter. Together, our results reveal an unexpected role of Fas/FasL signaling and offer a new insight into the role of these molecules in the regulation of immune tolerance.

Keywords: CD8; CD95; Fas; FasL; double negative T cell; tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoantigens / immunology
  • Autoantigens / metabolism*
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / transplantation
  • Cells, Cultured
  • Down-Regulation
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / immunology
  • Fas Ligand Protein / metabolism*
  • Immune Tolerance*
  • Kinetics
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Signal Transduction
  • fas Receptor / genetics
  • fas Receptor / immunology
  • fas Receptor / metabolism*

Substances

  • Autoantigens
  • CD8 Antigens
  • Fas Ligand Protein
  • Fas protein, mouse
  • Fasl protein, mouse
  • fas Receptor