title: Infusion of Sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate-Conjugated MOG35-55-Coupled Spleen Cells Effectively Prevents and Reverses Experimental Autoimmune Encephalomyelitis in Mice.
abstract: In this study, we have evaluated our recently developed method for antigen-cell coupling using sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) heterobifunctional crosslinker in prevention and reversal of experimental autoimmune encephalomyelitis (EAE). We demonstrate that infusion of MOG35-55-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 naïve syngeneic mice renders the recipient mice resistant to EAE induction. Unexpectedly, CD4+ T cell proliferation is similar upon ex vivo stimulation by MOG35-55 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 MOG35-55-responding IFN-γ-producing Th1 cells. These findings suggest that MOG-SP treatment induces EAE protective MOG35-55-specific regulatory T cells and suppresses EAE pathogenic Th17 and Th1 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.
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China ; Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Xia
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007114:Immunization; D018796:Immunoconjugates / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D008301:Maleimides; D051379:Mice; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D018796:Immunoconjugates; D008301:Maleimides; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C071675:sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate