title: 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.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, P R China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Yao
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Han
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liang
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D000068717:Glatiramer Acetate; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D011485:Protein Binding; D014611:Vaccination
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; C032907:Q surface antigens; D054353:Perforin; D000068717:Glatiramer Acetate; D016264:Dextran Sulfate