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Deletional tolerance mediated by extrathymic Aire-expressing cells.

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.

Pubmed ID: 18687966

Authors

  • Gardner JM
  • Devoss JJ
  • Friedman RS
  • Wong DJ
  • Tan YX
  • Zhou X
  • Johannes KP
  • Su MA
  • Chang HY
  • Krummel MF
  • Anderson MS

Journal

Science (New York, N.Y.)

Publication Data

August 8, 2008

Associated Grants

  • Agency: NIAID NIH HHS, Id: K08 AI076429
  • Agency: NIAID NIH HHS, Id: K08 AI076429-05
  • Agency: NIAID NIH HHS, Id: P01 AI035297
  • Agency: NIAID NIH HHS, Id: P01 AI035297-150009
  • Agency: NIAID NIH HHS, Id: P01 AI035297-159001
  • Agency: NIAID NIH HHS, Id: P01 AI035297-160009
  • Agency: NIAID NIH HHS, Id: P01 AI035297-169001
  • Agency: NIAID NIH HHS, Id: P01 AI035297-170009
  • Agency: NIAID NIH HHS, Id: P01 AI035297-179001
  • Agency: NIDDK NIH HHS, Id: P30 DK063720
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-05
  • Agency: NIGMS NIH HHS, Id: T32 GM007618

Mesh Terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Autoantigens
  • Autoimmunity
  • Cell Proliferation
  • Epithelial Cells
  • Gene Expression Regulation
  • Glucose-6-Phosphatase
  • Lymph Nodes
  • Lymphoid Tissue
  • Mice
  • Mice, Transgenic
  • Proteins
  • Self Tolerance
  • Spleen
  • Stromal Cells
  • T-Lymphocytes
  • Thymus Gland
  • Transcription Factors
  • Transcription, Genetic