Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa‐1‐restricted CD8+ regulatory cells. Issue 1 (7th November 2012)

• Record Type: Journal Article
• Authors: Yao, Yunliang; Han, Wenzheng; Liang, Jingjing; Ji, Jian; Wang, Jianli; Cantor, Harvey; Lu, Linrong
• Is Part Of: European journal of immunology. Volume 43:Issue 1(2013:Jan.)
• Page Start: 125
• Page End: 136
• Publication Date: 2012-11-07
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242758
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>