Infusion of Sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate-Conjugated MOG_(35-55)-Coupled Spleen Cells Effectively Prevents and Reverses Experimental Autoimmune Encephalomyelitis in Mice

摘要

In this study, we have evaluated our recently developed method for antigen-cell coupling using sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-l-carboxylate (sulfo-SMCC) heterobifunctional crosslinker in prevention and reversal of experimental autoimmune encephalomyelitis (EAE). We demonstrate that infusion of MOG_(35-55)-coupled spleen cells (MOG-SP) significantly prevents and reverses EAE. Further studies show that the protected animals exhibit significantly delayed EAE upon EAE reinduction. Moreover, adoptive transfer of CD4~+ T cells from the protected mice to naive syngeneic mice renders the recipient mice resistant to EAE induction. Unexpectedly, CD4~+ T cell proliferation is similar upon ex vivo stimulation by MOG_(35-55) amongst all groups. However, further analysis of those proliferating CD4~+ T cells shows remarkable differences in Foxp3+ regulatory T cells (70% in MOG-SP groups versus 10-25% in control groups) and in IL-17+ cells (2-3% in MOG-SP groups versus 6-9% in control groups). In addition, we discover that MOG-SP treatment also significantly attenuates MOG_(35-55) -responding IFN-y-producing Thl cells. These findings suggest that MOG-SP treatment induces EAE protective MOG_(35-55)-specific regulatory T cells and suppresses EAE pathogenic Thl7 and Thl cells. Our study provides a novel approach for antigen-based EAE immunotherapy, which can potentially be translated into clinical application for immunotherapy of multiple sclerosis.