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J Exp Med. 2010 Apr 12;207(4):681-8. doi: 10.1084/jem.20092465. Epub 2010 Mar 22.

Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation.

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  • 1Department of Microbiology and Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Abstract

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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PMID:
20308365
[PubMed - indexed for MEDLINE]
PMCID:
PMC2856027
Free PMC Article

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