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

Eur J Immunol. 2013 Jan;43(1):125-36. doi: 10.1002/eji.201242758. Epub 2012 Nov 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / 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*
  • Peptides / immunology
  • Perforin / metabolism
  • Protein Binding
  • Vaccination


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