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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. Copyright © 2021 Flores-Mendoza, Rodríguez-Rodríguez, Rubio, Madera-Salcedo, Rosetti and Crispín.

Citation

Giovanna Flores-Mendoza, Noé Rodríguez-Rodríguez, Rosa M Rubio, Iris K Madera-Salcedo, Florencia Rosetti, José C Crispín. Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens. Frontiers in immunology. 2021;12:635862

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PMID: 33841416

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