Frontiers in Immunology (Mar 2021)

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

  • Giovanna Flores-Mendoza,
  • Giovanna Flores-Mendoza,
  • Noé Rodríguez-Rodríguez,
  • Rosa M. Rubio,
  • Iris K. Madera-Salcedo,
  • Florencia Rosetti,
  • José C. Crispín,
  • José C. Crispín

DOI
https://doi.org/10.3389/fimmu.2021.635862
Journal volume & issue
Vol. 12

Abstract

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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.

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