Research ArticleTYPE 1 DIABETES

Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes

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Science Immunology  18 Nov 2016:
Vol. 1, Issue 5, eaai7793
DOI: 10.1126/sciimmunol.aai7793

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Exhausting autoimmunity

Checkpoint inhibitors have revolutionized cancer immunotherapy, allowing potentially exhausted tumor-reactive T cells to attack the tumor. However, in the case of autoimmunity, exhausted T cells may be the answer to stopping the disease. Long et al. report that, in type 1 diabetics treated with the anti-CD3 monoclonal antibody teplizumab, CD8 T cells with features of exhausted T cells are associated with best response to treatment. These cells recognized a broad spectrum of autoantigens and proliferated at a lower level ex vivo, yet their exhausted phenotype was not terminal because stimulating these cells with a ligand for the inhibitory receptor TIGIT further down-regulated their activation. These data suggest inducing T cell exhaustion as a potential therapeutic approach for type 1 diabetes.