Publication Date:
2008-08-09
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gardner, James M -- Devoss, Jason J -- Friedman, Rachel S -- Wong, David J -- Tan, Ying X -- Zhou, Xuyu -- Johannes, Kellsey P -- Su, Maureen A -- Chang, Howard Y -- Krummel, Matthew F -- Anderson, Mark S -- K08 AI076429/AI/NIAID NIH HHS/ -- K08 AI076429-05/AI/NIAID NIH HHS/ -- P01 AI035297/AI/NIAID NIH HHS/ -- P01 AI035297-150009/AI/NIAID NIH HHS/ -- P01 AI035297-159001/AI/NIAID NIH HHS/ -- P01 AI035297-160009/AI/NIAID NIH HHS/ -- P01 AI035297-169001/AI/NIAID NIH HHS/ -- P01 AI035297-170009/AI/NIAID NIH HHS/ -- P01 AI035297-179001/AI/NIAID NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- P30 DK063720-05/DK/NIDDK NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 8;321(5890):843-7. doi: 10.1126/science.1159407.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes Center, University of California San Francisco (UCSF), San Francisco, CA 94122, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18687966" target="_blank"〉PubMed〈/a〉
Keywords:
Adoptive Transfer
;
Animals
;
Antigen Presentation
;
Autoantigens/genetics/*immunology
;
Autoimmunity
;
Cell Proliferation
;
Epithelial Cells/immunology
;
Gene Expression Regulation
;
Glucose-6-Phosphatase/immunology
;
Lymph Nodes/cytology/*immunology/metabolism
;
Lymphoid Tissue/*cytology/immunology/*metabolism
;
Mice
;
Mice, Transgenic
;
Proteins/immunology
;
*Self Tolerance
;
Spleen/cytology/immunology/metabolism
;
Stromal Cells/immunology/metabolism
;
T-Lymphocytes/*immunology
;
Thymus Gland/cytology/immunology
;
Transcription Factors/genetics/*metabolism
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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