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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
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 th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516839/ https://www.ncbi.nlm.nih.gov/pubmed/26258148 http://dx.doi.org/10.1155/2015/129682 |
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author | Zhang, Lanfang Guo, Yixian Xia, Chang-Qing |
author_facet | Zhang, Lanfang Guo, Yixian Xia, Chang-Qing |
author_sort | Zhang, Lanfang |
collection | PubMed |
description | 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 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 naïve 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-γ-producing Th1 cells. These findings suggest that MOG-SP treatment induces EAE protective MOG(35–55)-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. |
format | Online Article Text |
id | pubmed-4516839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-45168392015-08-09 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 Zhang, Lanfang Guo, Yixian Xia, Chang-Qing J Immunol Res Research Article 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 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 naïve 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-γ-producing Th1 cells. These findings suggest that MOG-SP treatment induces EAE protective MOG(35–55)-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. Hindawi Publishing Corporation 2015 2015-07-14 /pmc/articles/PMC4516839/ /pubmed/26258148 http://dx.doi.org/10.1155/2015/129682 Text en Copyright © 2015 Lanfang Zhang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Lanfang Guo, Yixian Xia, Chang-Qing 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516839/ https://www.ncbi.nlm.nih.gov/pubmed/26258148 http://dx.doi.org/10.1155/2015/129682 |
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