Altered Gut Microbiota Activate and Expand Insulin B15-23-Reactive CD8+ T Cells.

ABSTRACT: Insulin is a major autoantigen in type 1 diabetes, targeted by both CD8 and CD4 T cells. We studied an insulin-reactive T-cell receptor (TCR) α-chain transgenic NOD mouse on a TCRCα and proinsulin 2 (PI2)-deficient background, designated as A22Cα^-/-PI2^-/- NOD mice. These mice develop a low incidence of autoimmune diabetes. To test the role of gut microbiota on diabetes development in this model system, we treated the A22Cα^-/-PI2^-/- NOD mice with enrofloxacin, a broad-spectrum antibiotic. The treatment led to male mice developing accelerated diabetes. We found that enrofloxacin increased the frequency of the insulin-reactive CD8+ T cells and activated the cells in the Peyer's patches and pancreatic lymph nodes, together with inductio

SUBMITTER: Pearson JA 

PROVIDER: S-EPMC6477900 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature