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Revealing the specificity of regulatory T cells in murine autoimmune diabetes.


ABSTRACT: Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT. T cell receptor (TCR) repertoire profiling demonstrated that islet Treg clonotypes are expanded in the islets, suggesting localized antigen-driven expansion in inflamed islets. To determine their specificity, we captured TCR?? pairs from islet Tregs using single-cell TCR sequencing and found direct evidence that some of these TCRs were specific for islet-derived antigens including insulin B:9-23 and proinsulin. Consistently, insulin B:9-23 tetramers readily detected insulin-specific Tregs in the islets of NOD mice. Lastly, islet Tregs from prediabetic NOD mice were effective at preventing diabetes in Treg-deficient NOD.CD28-/- recipients. These results provide a glimpse into the specificities of Tregs in a natural repertoire that are crucial for opposing the progression of autoimmune diabetes.

SUBMITTER: Spence A 

PROVIDER: S-EPMC5960284 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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Revealing the specificity of regulatory T cells in murine autoimmune diabetes.

Spence Allyson A   Purtha Whitney W   Tam Janice J   Dong Shen S   Kim Youmin Y   Ju Chia-Hsin CH   Sterling Teague T   Nakayama Maki M   Robinson William H WH   Bluestone Jeffrey A JA   Anderson Mark S MS   Tang Qizhi Q  

Proceedings of the National Academy of Sciences of the United States of America 20180430 20


Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with highe  ...[more]

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