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 ORCID: https://orcid.org/0000-0002-2812-8845 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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Abstract

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:	05 May 2023 11:39
URI:	https://orca.cardiff.ac.uk/id/eprint/96317

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