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

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.

Keywords::

• Autoimmunity
• EAE
• monocyte
• superantigen
• T cell
• antigen-specific suppression

Acknowledgements

We would thank to Kylie Price and Evelyn Spittle for their technical support. This research was supported by: the Lottery Health Research Committee (NZ), the Health Research Council (NZ) and the Wellington Medical Research Foundation (NZ).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.