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: Lanfang Zhang, Yixian Guo, Chang-Qing Xia
• Journal: Journal of immunology research (J Immunol Res) Vol. 2015 Pg. 129682 ( 2015) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 26258148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Immunoconjugates
• Maleimides
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments
• myelin oligodendrocyte glycoprotein (35-55)
• sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate

Topics

• Adoptive Transfer
• Animals
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Encephalomyelitis, Autoimmune, Experimental (diagnosis, immunology, prevention & control, therapy)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Immunization
• Immunoconjugates (administration & dosage)
• Lymphocyte Activation
• Maleimides
• Mice
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments
• Severity of Illness Index
• Spleen (cytology, immunology)
• T-Lymphocyte Subsets (immunology, metabolism)