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Deletional Tolerance Mediated by Extrathymic Aire-Expressing Cells
James M. Gardner,1Jason J. DeVoss,1Rachel S. Friedman,2David J. Wong,3Ying X. Tan,1Xuyu Zhou,1Kellsey P. Johannes,1Maureen A. Su,1,4Howard Y. Chang,3Matthew F. Krummel,2Mark S. Anderson1*
The prevention of autoimmunity requires the elimination of self-reactiveT cells during their development and maturation. The expressionof diverse self-antigens by stromal cells in the thymus is essentialto this process and depends, in part, on the activity of theautoimmune regulator (Aire) gene. Here we report the identificationof extrathymic Aire-expressing cells (eTACs) resident withinthe secondary lymphoid organs. These stromally derived eTACsexpress a diverse array of distinct self-antigens and are capableof interacting with and deleting naïve autoreactive T cells.Using two-photon microscopy, we observed stable antigen-specificinteractions between eTACs and autoreactive T cells. We proposethat such a secondary network of self-antigen–expressingstromal cells may help reinforce immune tolerance by preventingthe maturation of autoreactive T cells that escape thymic negativeselection.
1 Diabetes Center, University of California San Francisco (UCSF), San Francisco, CA 94122, USA. 2 Department of Pathology, UCSF, San Francisco, CA 94143, USA. 3 Program in Epithelial Biology, Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA. 4 Department of Pediatrics, UCSF, San Francisco, CA 94122, USA.
* To whom correspondence should be addressed. E-mail: manderson{at}diabetes.ucsf.edu
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Bruno Kyewski (8 August 2008) Science321 (5890), 776.
[DOI: 10.1126/science.1162966] |Summary »|Full Text »|PDF »
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