Journal
SCIENCE
Volume 321, Issue 5890, Pages 843-847Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1159407
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Funding
- NIAID NIH HHS [K08 AI076429-05, P01 AI035297-160009, K08 AI076429, P01 AI035297-179001, P01 AI035297-150009, P01 AI035297, P01 AI035297-169001, P01 AI035297-159001, P01 AI035297-170009] Funding Source: Medline
- NIDDK NIH HHS [P30 DK063720, P30 DK063720-05] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007618] Funding Source: Medline
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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 naive 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.
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