Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa‐1‐restricted CD8+ regulatory cells
Copyright policy )Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa‐1‐restricted CD8+ regulatory cells
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.
- Harvard University United States
- Zhejiang Ocean University China (People's Republic of)
- Dana-Farber Cancer Institute United States
- Women's Hospital School Of Medicine Zhejiang University China (People's Republic of)
- Zhejiang Sci-Tech University China (People's Republic of)
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Immunosuppression Therapy, Perforin, Dextran Sulfate, Histocompatibility Antigens Class I, Vaccination, Glatiramer Acetate, CD8-Positive T-Lymphocytes, Colitis, Inflammatory Bowel Diseases, Mice, Inbred C57BL, Disease Models, Animal, Mice, Animals, Humans, Peptides, Cells, Cultured, Protein Binding
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Immunosuppression Therapy, Perforin, Dextran Sulfate, Histocompatibility Antigens Class I, Vaccination, Glatiramer Acetate, CD8-Positive T-Lymphocytes, Colitis, Inflammatory Bowel Diseases, Mice, Inbred C57BL, Disease Models, Animal, Mice, Animals, Humans, Peptides, Cells, Cultured, Protein Binding
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