Published in

American Association for the Advancement of Science, Science, 5890(321), p. 843-847, 2008

DOI: 10.1126/science.1159407

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Deletional Tolerance Mediated by Extrathymic Aire-Expressing Cells*

This paper is available in a repository.
This paper is available in a repository.

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Abstract

The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. The expression of diverse self-antigens by stromal cells in the thymus is essential to this process and depends, in part, on the activity of the autoimmune regulator ( Aire ) gene. Here we report the identification of extrathymic Aire -expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally derived eTACs express a diverse array of distinct self-antigens and are capable of interacting with and deleting naïve autoreactive T cells. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen–expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection.