Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa-1-restricted CD8⁺ regulatory cells.

Yunliang Yao, Wenzheng Han, Jingjing Liang, Jian Ji, Jianli Wang, Harvey Cantor, Linrong Lu

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, P R China.

European journal of immunology 2013 Jan

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Inflammatory bowel diseases (IBDs) are complex multifactorial immunological disorders characterized by dysregulated immune reactivity in the intestine. Here, we investigated the contribution of Qa-1-restricted CD8(+) Treg cells in regulating experimental IBD in mice. We found that CD8(+) T cells induced by T-cell vaccination ameliorated the pathological manifestations of dextran sulfate sodium induced IBD when adoptively transferred into IBD mice. In addition, CD8(+) cell suppressive activity was induced by vaccination with glatiramer acetate (GA), an FDA-approved drug for multiple sclerosis (MS). We next showed that GA-induced CD8(+) Treg cells worked in a Qa-1-dependent manner and their suppressive activity depends on perforin-mediated cytotoxicity. Finally, we confirmed the role of CD4(+) T cells in dextran sulfate sodium induced colitis progression, and clarified that GA-induced CD8(+) T cells exerted their therapeutic effects on colitis by targeting pathogenic CD4(+) T cells. Our results reveal a new regulatory role of Qa-1-restricted CD8(+) Treg cells in IBD and suggest their induction by GA vaccination as a potential therapeutic approach to IBD. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Yunliang Yao, Wenzheng Han, Jingjing Liang, Jian Ji, Jianli Wang, Harvey Cantor, Linrong Lu. Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa-1-restricted CD8⁺ regulatory cells. European journal of immunology. 2013 Jan;43(1):125-36