A modified superantigen rescues Ly6G- CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE

Research output: Contribution to journalArticle

Abstract

In a previous study, we showed that the Ly6G(-)CD11b(+) blood monocytes residing in naïve mice are intrinsically immunosuppressive and that loss of this suppressive function may contribute to the development of autoimmunity in experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis. Here we report that mice treated with a modified superantigen coupled to myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide (DM-MOG(35-55)) suppressed the development of EAE. The treatment was associated with impaired MOG(35-55)-specific T cell proliferation and a decrease in IL-17 and IFNγ production in the draining lymph nodes. Analysis of circulating blood immune cells showed that the suppressor function of Ly6G(-)CD11b(+) blood monocytes was reduced in EAE mice, but was restored in mice treated with DM-MOG(35-55). Importantly, adoptive transfer of blood CD11b(+)Ly6G(-) cells isolated from DM-MOG(35-55)-treated mice protected recipient mice from developing EAE. Together, these results show that DM coupled to the auto-antigen MOG(35-55): 1) suppresses EAE via antigen-specific suppression of T cell responses, and 2) re-establishes suppressor function of Ly6G(-)CD11b(+) blood monocytes. Auto-antigens coupled to DM could therefore represent a new therapeutic approach for controlling inappropriate inflammation in autoimmune diseases such as multiple sclerosis by inducing antigen-specific T cell suppression.

Details

Authors
External organisations
  • Novo Nordisk A/S
  • Malaghan Institute of Medical Research
Research areas and keywords

Keywords

  • Adoptive Transfer, Animals, Antigens, Ly/metabolism, Bacterial Toxins/chemistry, CD11b Antigen/metabolism, Encephalomyelitis, Autoimmune, Experimental/immunology, Epitopes/immunology, Exotoxins/chemistry, Lymphocyte Activation/immunology, Mice, Monocytes/immunology, Myelin-Oligodendrocyte Glycoprotein/chemistry, Peptide Fragments/chemistry, Superantigens/immunology, T-Lymphocyte Subsets/immunology
Original languageEnglish
Pages (from-to)269-78
JournalAutoimmunity
Volume46
Issue number4
Publication statusPublished - 2013 Jun
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes