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


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.

SUBMITTER: Flores-Mendoza G 

PROVIDER: S-EPMC8024570 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Flores-Mendoza Giovanna G   Rodríguez-Rodríguez Noé N   Rubio Rosa M RM   Madera-Salcedo Iris K IK   Rosetti Florencia F   Crispín José C JC  

Frontiers in immunology 20210324


Activation of self-reactive CD8<sup>+</sup> T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of <i>Fas</i> and <i>Fasl</i> causes the accumulation of double-negative (DN; CD3<sup>+</sup> TCR-αβ<sup>+</sup> CD4<sup>-</sup> CD8<sup>-</sup>) T cells that have been proposed to derive from CD8<sup>+</sup> cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and  ...[more]

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