期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 43, 期 1, 页码 125-136出版社
WILEY
DOI: 10.1002/eji.201242758
关键词
CD8+Treg; Colitis; Inflammation; Qa-1
类别
资金
- National Natural Science Foundation of China [30972724, 31070782]
- National Basic Research Program of China (973 Program) [2011CB944100, 2012CB945004]
- Zhejiang Provincial Natural Science Foundation of China [R2090202]
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.
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