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: Yunliang Yao, Wenzheng Han, Jingjing Liang, Jian Ji, Jianli Wang, Harvey Cantor, Linrong Lu
• Journal: European journal of immunology (Eur J Immunol) Vol. 43 Issue 1 Pg. 125-36 (Jan 2013) ISSN: 1521-4141 [Electronic] Germany
• PMID: 23002042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Histocompatibility Antigens Class I
• Peptides
• Q surface antigens
• Perforin
• Glatiramer Acetate
• Dextran Sulfate

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Colitis (chemically induced, drug therapy, immunology)
• Cytotoxicity, Immunologic
• Dextran Sulfate (administration & dosage)
• Disease Models, Animal
• Glatiramer Acetate
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Immunosuppression Therapy
• Inflammatory Bowel Diseases (therapy)
• Mice
• Mice, Inbred C57BL
• Peptides (administration & dosage, immunology)
• Perforin (metabolism)
• Protein Binding
• Vaccination