Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.

Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice tha...

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Autores principales:	Emilie Franck, Carole Bonneau, Laetitia Jean, Jean-Paul Henry, Yann Lacoume, Anna Salvetti, Olivier Boyer, Sahil Adriouch
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8724d9f9a2154f7da79f0107e5c6497b
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spelling	oai:doaj.org-article:8724d9f9a2154f7da79f0107e5c6497b2021-11-18T07:19:48ZImmunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.1932-620310.1371/journal.pone.0036444https://doaj.org/article/8724d9f9a2154f7da79f0107e5c6497b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22570714/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4(+) T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8(+) T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8(+) tolerance in SM-Ova mice. We show herein that Ova-specific CD8(+) T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8(+) T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8(+) T cells.Emilie FranckCarole BonneauLaetitia JeanJean-Paul HenryYann LacoumeAnna SalvettiOlivier BoyerSahil AdriouchPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36444 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emilie Franck Carole Bonneau Laetitia Jean Jean-Paul Henry Yann Lacoume Anna Salvetti Olivier Boyer Sahil Adriouch Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.
description	Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4(+) T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8(+) T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8(+) tolerance in SM-Ova mice. We show herein that Ova-specific CD8(+) T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8(+) T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8(+) T cells.
format	article
author	Emilie Franck Carole Bonneau Laetitia Jean Jean-Paul Henry Yann Lacoume Anna Salvetti Olivier Boyer Sahil Adriouch
author_facet	Emilie Franck Carole Bonneau Laetitia Jean Jean-Paul Henry Yann Lacoume Anna Salvetti Olivier Boyer Sahil Adriouch
author_sort	Emilie Franck
title	Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.
title_short	Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.
title_full	Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.
title_fullStr	Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.
title_full_unstemmed	Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.
title_sort	immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive cd8+ t cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8724d9f9a2154f7da79f0107e5c6497b
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Immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells.

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