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Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla

The thymic medulla is dedicated for purging the T-cell receptor (TCR) repertoire of self-reactive specificities. Medullary thymic epithelial cells (mTECs) play a pivotal role in this process because they express numerous peripheral tissue-restricted self-antigens. Although it is well known that medu...

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Autores principales: Irla, Magali, Guerri, Lucia, Guenot, Jeanne, Sergé, Arnauld, Lantz, Olivier, Liston, Adrian, Imhof, Beat A., Palmer, Ed, Reith, Walter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531460/
https://www.ncbi.nlm.nih.gov/pubmed/23300712
http://dx.doi.org/10.1371/journal.pone.0052591
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author Irla, Magali
Guerri, Lucia
Guenot, Jeanne
Sergé, Arnauld
Lantz, Olivier
Liston, Adrian
Imhof, Beat A.
Palmer, Ed
Reith, Walter
author_facet Irla, Magali
Guerri, Lucia
Guenot, Jeanne
Sergé, Arnauld
Lantz, Olivier
Liston, Adrian
Imhof, Beat A.
Palmer, Ed
Reith, Walter
author_sort Irla, Magali
collection PubMed
description The thymic medulla is dedicated for purging the T-cell receptor (TCR) repertoire of self-reactive specificities. Medullary thymic epithelial cells (mTECs) play a pivotal role in this process because they express numerous peripheral tissue-restricted self-antigens. Although it is well known that medulla formation depends on the development of single-positive (SP) thymocytes, the mechanisms underlying this requirement are incompletely understood. We demonstrate here that conventional SP CD4(+) thymocytes bearing autoreactive TCRs drive a homeostatic process that fine-tunes medullary plasticity in adult mice by governing the expansion and patterning of the medulla. This process exhibits strict dependence on TCR-reactivity with self-antigens expressed by mTECs, as well as engagement of the CD28-CD80/CD86 costimulatory axis. These interactions induce the expression of lymphotoxin α in autoreactive CD4(+) thymocytes and RANK in mTECs. Lymphotoxin in turn drives mTEC development in synergy with RANKL and CD40L. Our results show that Ag-dependent interactions between autoreactive CD4(+) thymocytes and mTECs fine-tune homeostasis of the medulla by completing the signaling axes implicated in mTEC expansion and medullary organization.
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spelling pubmed-35314602013-01-08 Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla Irla, Magali Guerri, Lucia Guenot, Jeanne Sergé, Arnauld Lantz, Olivier Liston, Adrian Imhof, Beat A. Palmer, Ed Reith, Walter PLoS One Research Article The thymic medulla is dedicated for purging the T-cell receptor (TCR) repertoire of self-reactive specificities. Medullary thymic epithelial cells (mTECs) play a pivotal role in this process because they express numerous peripheral tissue-restricted self-antigens. Although it is well known that medulla formation depends on the development of single-positive (SP) thymocytes, the mechanisms underlying this requirement are incompletely understood. We demonstrate here that conventional SP CD4(+) thymocytes bearing autoreactive TCRs drive a homeostatic process that fine-tunes medullary plasticity in adult mice by governing the expansion and patterning of the medulla. This process exhibits strict dependence on TCR-reactivity with self-antigens expressed by mTECs, as well as engagement of the CD28-CD80/CD86 costimulatory axis. These interactions induce the expression of lymphotoxin α in autoreactive CD4(+) thymocytes and RANK in mTECs. Lymphotoxin in turn drives mTEC development in synergy with RANKL and CD40L. Our results show that Ag-dependent interactions between autoreactive CD4(+) thymocytes and mTECs fine-tune homeostasis of the medulla by completing the signaling axes implicated in mTEC expansion and medullary organization. Public Library of Science 2012-12-27 /pmc/articles/PMC3531460/ /pubmed/23300712 http://dx.doi.org/10.1371/journal.pone.0052591 Text en © 2012 Irla et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Irla, Magali
Guerri, Lucia
Guenot, Jeanne
Sergé, Arnauld
Lantz, Olivier
Liston, Adrian
Imhof, Beat A.
Palmer, Ed
Reith, Walter
Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla
title Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla
title_full Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla
title_fullStr Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla
title_full_unstemmed Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla
title_short Antigen Recognition By Autoreactive Cd4(+) Thymocytes Drives Homeostasis Of The Thymic Medulla
title_sort antigen recognition by autoreactive cd4(+) thymocytes drives homeostasis of the thymic medulla
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531460/
https://www.ncbi.nlm.nih.gov/pubmed/23300712
http://dx.doi.org/10.1371/journal.pone.0052591
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