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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...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
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.
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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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