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Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation
Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856027/ https://www.ncbi.nlm.nih.gov/pubmed/20308365 http://dx.doi.org/10.1084/jem.20092465 |
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author | Cohen, Jarish N. Guidi, Cynthia J. Tewalt, Eric F. Qiao, Hui Rouhani, Sherin J. Ruddell, Alanna Farr, Andrew G. Tung, Kenneth S. Engelhard, Victor H. |
author_facet | Cohen, Jarish N. Guidi, Cynthia J. Tewalt, Eric F. Qiao, Hui Rouhani, Sherin J. Ruddell, Alanna Farr, Andrew G. Tung, Kenneth S. Engelhard, Victor H. |
author_sort | Cohen, Jarish N. |
collection | PubMed |
description | Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance. |
format | Text |
id | pubmed-2856027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28560272010-10-12 Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation Cohen, Jarish N. Guidi, Cynthia J. Tewalt, Eric F. Qiao, Hui Rouhani, Sherin J. Ruddell, Alanna Farr, Andrew G. Tung, Kenneth S. Engelhard, Victor H. J Exp Med Brief Definitive Report Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance. The Rockefeller University Press 2010-04-12 /pmc/articles/PMC2856027/ /pubmed/20308365 http://dx.doi.org/10.1084/jem.20092465 Text en © 2010 Cohen et al. 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.rupress.org/terms). 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 Cohen, Jarish N. Guidi, Cynthia J. Tewalt, Eric F. Qiao, Hui Rouhani, Sherin J. Ruddell, Alanna Farr, Andrew G. Tung, Kenneth S. Engelhard, Victor H. Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation |
title | Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation |
title_full | Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation |
title_fullStr | Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation |
title_full_unstemmed | Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation |
title_short | Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation |
title_sort | lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via aire-independent direct antigen presentation |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856027/ https://www.ncbi.nlm.nih.gov/pubmed/20308365 http://dx.doi.org/10.1084/jem.20092465 |
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