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

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 dec...

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Main Authors: Giovanna Flores-Mendoza, Noé Rodríguez-Rodríguez, Rosa M. Rubio, Iris K. Madera-Salcedo, Florencia Rosetti, José C. Crispín
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.635862/full
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author Giovanna Flores-Mendoza
Giovanna Flores-Mendoza
Noé Rodríguez-Rodríguez
Rosa M. Rubio
Iris K. Madera-Salcedo
Florencia Rosetti
José C. Crispín
José C. Crispín
author_facet Giovanna Flores-Mendoza
Giovanna Flores-Mendoza
Noé Rodríguez-Rodríguez
Rosa M. Rubio
Iris K. Madera-Salcedo
Florencia Rosetti
José C. Crispín
José C. Crispín
author_sort Giovanna Flores-Mendoza
collection DOAJ
description 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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spelling doaj.art-4184c604a5894975b0755b21e4f986632022-12-21T22:41:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.635862635862Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-AntigensGiovanna Flores-Mendoza0Giovanna Flores-Mendoza1Noé Rodríguez-Rodríguez2Rosa M. Rubio3Iris K. Madera-Salcedo4Florencia Rosetti5José C. Crispín6José C. Crispín7Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM), Mexico City, MexicoDepartamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoDepartamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoEscuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, MexicoActivation 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.635862/fullCD8CD95FasFasLtolerancedouble negative T cell
spellingShingle Giovanna Flores-Mendoza
Giovanna Flores-Mendoza
Noé Rodríguez-Rodríguez
Rosa M. Rubio
Iris K. Madera-Salcedo
Florencia Rosetti
José C. Crispín
José C. Crispín
Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
Frontiers in Immunology
CD8
CD95
Fas
FasL
tolerance
double negative T cell
title Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
title_full Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
title_fullStr Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
title_full_unstemmed Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
title_short Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens
title_sort fas fasl signaling regulates cd8 expression during exposure to self antigens
topic CD8
CD95
Fas
FasL
tolerance
double negative T cell
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.635862/full
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