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Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice

Tai, Ningwen, Peng, Jian, Liu, Fuqiang, Gulden, Elke, Hu, Youjia, Zhang, Xiaojun, Chen, Li, Wong, Florence Susan and Wen, Li 2016. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice. Journal of Experimental Medicine 213 (10) , p. 2129. 10.1084/jem.20160526

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Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)–reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8+ T cell–mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8+ T cells can be regulated by innate immunity and the gut microbiota.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: Rockefeller University Press
ISSN: 0022-1007
Funders: JDRF
Date of First Compliant Deposit: 21 November 2016
Date of Acceptance: 5 August 2016
Last Modified: 22 Jan 2019 14:23

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