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


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.

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  1. Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
  2. Virologie et Immunologie Moleculaires UR892, INRA, Domaine de Vilvert, F-78352 Jouy-en-Josas, France.
  3. Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts 02115, USA.
  4. Ludwig Institute for Cancer Research, Melbourne Branch, Post Office Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
  5. 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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