Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity.

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ID: 71715
2019
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Ranked #26 of 292 articles by views in Proceedings of the National Academy of Sciences of the United States of America

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Abstract
Activation of self-reactive T cells is a major driver to autoimmunity and is suppressed by mechanisms of regulation. In a humanized model of autoimmune thyroiditis, we investigated the mechanism underlying break of tolerance. Here, we found that a human TCR specific for the self-antigen thyroid peroxidase (TPO) is positively selected in the thymus of RAG KO mice on both T effector (T) and T regulatory (T) CD4Foxp3 cells. In vivo T are present in all immune organs, whereas the TPO-specific T are present in all lymphoid organs with the exception of the thyroid-draining lymph nodes. We suggest that the presence of TPO in the thyroid draining lymph nodes induces the activation of T and the depletion of T via activation-induced cell death (AICD). Our findings provide insights on the failure of the mechanisms of immune tolerance, with potential implications in designing immunotherapeutic strategies.
Reference Key
badami2019activationinducedproceedings Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Badami, Ester;Cexus, Olivier N F;Quaratino, Sonia;
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2019
DOI
201910281
URL
Keywords
autoimmunity tolerance regulatory t cells aicd

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