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

• Published in: Autoimmunity (Chur, Switzerland) Vol. 46; no. 4; pp. 269 - 278
• Main Authors: Slaney, Clare Y., Toker, Aras, Fraser, John D., Harper, Jacquie L., Bäckström, B. Thomas
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.06.2013; Taylor & Francis
• Subjects: Adoptive Transfer; Animals; antigen-specific suppression; Antigens, Ly - metabolism; Autoimmunity; Bacterial Toxins - chemistry; Bacterial Toxins - immunology; CD11b Antigen - metabolism; EAE; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - therapy; Epitopes - immunology; Exotoxins - chemistry; Exotoxins - immunology; Lymphocyte Activation - immunology; Mice; monocyte; Monocytes - immunology; Monocytes - metabolism; Myelin-Oligodendrocyte Glycoprotein - chemistry; Myelin-Oligodendrocyte Glycoprotein - immunology; Peptide Fragments - chemistry; Peptide Fragments - immunology; superantigen; Superantigens - immunology; T cell; T-Lymphocyte Subsets - immunology
• ISSN: 0891-6934; 1607-842X
• DOI: 10.3109/08916934.2013.767893

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 (MOG35-55) peptide (DM-MOG35-55) suppressed the development of EAE. The treatment was associated with impaired MOG35-55-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-MOG35-55. Importantly, adoptive transfer of blood CD11b+Ly6G− cells isolated from DM-MOG35-55-treated mice protected recipient mice from developing EAE. Together, these results show that DM coupled to the auto-antigen MOG35-55: 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.