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Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
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Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
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Journal Article
Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
2021
Overview
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.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Animals
/ Antigens
/ CD8
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ CD8-Positive T-Lymphocytes - transplantation
/ CD95
/ Fas
/ Fas Ligand Protein - genetics
/ Fas Ligand Protein - immunology
/ Fas Ligand Protein - metabolism
/ FasL
/ Kinetics
/ Mice
/ Mutation
