Journal Article

Deletional Tolerance Mediated by Extrathymic Aire-Expressing Cells

Friedman, Rachel S, Johannes, Kellsey P, Chang, Howard Y, DeVoss, Jason J, Gardner, James M, Su, Maureen A, Anderson, Mark S, Wong, David J, Tan, Ying X, Zhou, Xuyu, Krummel, Matthew F

2008

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adoptive Transfer / AIRE Protein / Animals / Antigen Presentation / Autoantigens / Autoantigens - genetics / Autoantigens - immunology / Autoimmune diseases / Autoimmunity / Biological and medical sciences / Cell Proliferation / Cellular biology / Diabetes / Endocrinology / Epithelial Cells - immunology / Fundamental and applied biological sciences. Psychology / Fundamental immunology / Gene expression / Gene Expression Regulation / genes / Genetics / Glucose-6-Phosphatase - immunology / Immunobiology / Immunological tolerance / Immunology / immunosuppression / Lymph nodes / Lymph Nodes - cytology / Lymph Nodes - immunology / Lymph Nodes - metabolism / Lymphoid Tissue - cytology / Lymphoid Tissue - immunology / Lymphoid Tissue - metabolism / Mice / Mice, Transgenic / microscopy / Proteins - immunology / Self Tolerance / Spleen / Spleen - cytology / Spleen - immunology / Spleen - metabolism / Stromal cells / Stromal Cells - immunology / Stromal Cells - metabolism / T lymphocytes / T-Lymphocytes - immunology / thymus gland / Thymus Gland - cytology / Thymus Gland - immunology / Transcription Factors - genetics / Transcription Factors - metabolism / Transcription, Genetic / Transgenes / Transgenic animals