A modified superantigen rescues Ly6G− CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE. (June 2013)

• Record Type: Journal Article
• Authors: Slaney, Clare Y.; Toker, Aras; Fraser, John D.; Harper, Jacquie L.; Bäckström, B. Thomas
• Is Part Of: Autoimmunity. Volume 46:Number 4(2013)
• Page Start: 269
• Page End: 278
• Publication Date: 2013-06
• Subjects: Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.3109/08916934.2013.767893
• Languages: English
• ISSNs: 0891-6934

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>In a previous study, we showed that the Ly6G<sup>− </sup>CD11b<sup>+</sup> 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<sub>35–55</sub>) peptide (DM-MOG<sub>35–55</sub>) suppressed the development of EAE. The treatment was associated with impaired MOG<sub>35–55</sub>-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<sup>− </sup>CD11b<sup>+</sup> blood monocytes was reduced in EAE mice, but was restored in mice treated with DM-MOG<sub>35–55</sub>. Importantly, adoptive transfer of blood CD11b<sup>+</sup>Ly6G<sup>− </sup> cells isolated from DM-MOG<sub>35–55</sub>-treated mice protected recipient mice from developing EAE. Together, these results show that DM coupled to the auto-antigen MOG<sub>35–55</sub>: 1) suppresses EAE via antigen-specific suppression of T cell responses, and 2) re-establishes suppressor function of Ly6G<sup>− </sup>CD11b<sup>+</sup> 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.</p> </abstract>