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

Abstract

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.