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

Journal of Experimental Medicine - Tập 207 Số 4 - Trang 681-688 - 2010
Jarish N. Cohen1,2, Cynthia J. Guidi1,2, Eric F. Tewalt1,2, Hui Qiao1,2, Sherin J. Rouhani1,2, Alanna Ruddell3,4, Andrew G. Farr3,4, Kenneth S. K. Tung1,2, Víctor H. Engelhard1,2
1Department of Microbiology and Carter Immunology Center and Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908
2Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908 1 and 2
3Department of Biological Structure, University of Washington, Seattle, WA 98195 3 and 4
4Fred Hutchinson Cancer Research Center and Department of Biological Structure, University of Washington, Seattle, WA 98195

Tóm tắt

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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