Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity.
Proc Natl Acad Sci U S A
; 116(52): 26788-26797, 2019 Dec 26.
Article
em En
| MEDLINE
| ID: mdl-31818938
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 (Teff) and T regulatory (Treg) CD4+Foxp3+ cells. In vivo Teff are present in all immune organs, whereas the TPO-specific Treg 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 Teff and the depletion of Treg 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.
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MEDLINE
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En
Ano de publicação:
2019
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Article