Article abstract
Nature Immunology 8, 181 - 190 (2006)
Published online: 31 December 2006 | doi:10.1038/ni1427
Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self
Je-Wook Lee1, Mathieu Epardaud1,2, Jing Sun1, Jessica E Becker1, Alexander C Cheng1, Ai-ris Yonekura1,3, Joan K Heath4 & Shannon J Turley1,5
Abstract
The intestinal epithelium functions to absorb nutrients and to protect the organism against microbes. To prevent autoimmune attack on this vital tissue, T cell tolerance to intestinal self-antigens must be established. Central tolerance mechanisms involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive thymocytes. The prevailing model for the induction of peripheral tolerance involves cross-presentation of tissue antigens by quiescent dendritic cells. Here we show that lymph node stromal cells present endogenously expressed PTAs to T cells. Moreover, antigen presentation by lymph node stroma is sufficient to induce primary activation and subsequent tolerance among CD8+ T cells. Thus, lymph node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peripheral repertoire of self-reactive T cells.
- Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
- Virologie et Immunologie Moleculaires UR892, INRA, Domaine de Vilvert, F-78352 Jouy-en-Josas, France.
- Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts 02115, USA.
- Ludwig Institute for Cancer Research, Melbourne Branch, Post Office Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
- Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence to: Shannon J Turley1,5 e-mail: shannon_turley@dfci.harvard.edu
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