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The thymic medulla: a unique microenvironment for intercellular self-antigen transfer
Central tolerance is shaped by the array of self-antigens expressed and presented by various types of thymic antigen-presenting cells (APCs). Depending on the overall signal quality and/or quantity delivered in these interactions, self-reactive thymocytes either apoptose or commit to the T regulator...
Autores principales: | , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715082/ https://www.ncbi.nlm.nih.gov/pubmed/19564355 http://dx.doi.org/10.1084/jem.20082449 |
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author | Koble, Christian Kyewski, Bruno |
author_facet | Koble, Christian Kyewski, Bruno |
author_sort | Koble, Christian |
collection | PubMed |
description | Central tolerance is shaped by the array of self-antigens expressed and presented by various types of thymic antigen-presenting cells (APCs). Depending on the overall signal quality and/or quantity delivered in these interactions, self-reactive thymocytes either apoptose or commit to the T regulatory cell lineage. The cellular and molecular complexity underlying these events has only recently been appreciated. We analyzed the ex vivo presentation of ubiquitous or tissue-restricted self-antigens by medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs), the two major APC types present in the medulla. We found that the ubiquitously expressed nuclear neo–self-antigen ovalbumin (OVA) was efficiently presented via major histocompatibility complex class II by mTECs and thymic DCs. However, presentation by DCs was highly dependent on antigen expression by TECs, and hemopoietic cells did not substitute for this antigen source. Accordingly, efficient deletion of OVA-specific T cells correlated with OVA expression by TECs. Notably, OVA was only presented by thymic but not peripheral DCs. We further demonstrate that thymic DCs are constitutively provided in situ with cytosolic as well as membrane-bound mTEC-derived proteins. The subset of DCs displaying transferred proteins was enriched in activated DCs, with these cells being most efficient in presenting TEC-derived antigens. These data provide evidence for a unique, constitutive, and unidirectional transfer of self-antigens within the thymic microenvironment, thus broadening the cellular base for tolerance induction toward promiscuously expressed tissue antigens. |
format | Text |
id | pubmed-2715082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27150822010-01-06 The thymic medulla: a unique microenvironment for intercellular self-antigen transfer Koble, Christian Kyewski, Bruno J Exp Med Brief Definitive Report Central tolerance is shaped by the array of self-antigens expressed and presented by various types of thymic antigen-presenting cells (APCs). Depending on the overall signal quality and/or quantity delivered in these interactions, self-reactive thymocytes either apoptose or commit to the T regulatory cell lineage. The cellular and molecular complexity underlying these events has only recently been appreciated. We analyzed the ex vivo presentation of ubiquitous or tissue-restricted self-antigens by medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs), the two major APC types present in the medulla. We found that the ubiquitously expressed nuclear neo–self-antigen ovalbumin (OVA) was efficiently presented via major histocompatibility complex class II by mTECs and thymic DCs. However, presentation by DCs was highly dependent on antigen expression by TECs, and hemopoietic cells did not substitute for this antigen source. Accordingly, efficient deletion of OVA-specific T cells correlated with OVA expression by TECs. Notably, OVA was only presented by thymic but not peripheral DCs. We further demonstrate that thymic DCs are constitutively provided in situ with cytosolic as well as membrane-bound mTEC-derived proteins. The subset of DCs displaying transferred proteins was enriched in activated DCs, with these cells being most efficient in presenting TEC-derived antigens. These data provide evidence for a unique, constitutive, and unidirectional transfer of self-antigens within the thymic microenvironment, thus broadening the cellular base for tolerance induction toward promiscuously expressed tissue antigens. The Rockefeller University Press 2009-07-06 /pmc/articles/PMC2715082/ /pubmed/19564355 http://dx.doi.org/10.1084/jem.20082449 Text en © 2009 Koble and Kyewski This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Koble, Christian Kyewski, Bruno The thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
title | The thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
title_full | The thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
title_fullStr | The thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
title_full_unstemmed | The thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
title_short | The thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
title_sort | thymic medulla: a unique microenvironment for intercellular self-antigen transfer |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715082/ https://www.ncbi.nlm.nih.gov/pubmed/19564355 http://dx.doi.org/10.1084/jem.20082449 |
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