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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3531460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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