Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
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.
J Immunol Res. 2015;2015:129682. doi: 10.1155/2015/129682. Epub 2015 Jul 14.
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.
在这项研究中，我们评估了我们最近使用磺基琥珀酰亚胺基-4-[N-马来酰亚胺甲基]环己烷-1-羧酸酯（sulfo-SMCC）异双功能交联剂在预防和逆转实验性自身免疫性脑脊髓炎（EAE）中开发的抗原细胞偶联方法。我们证明，MOG35-55 偶联的脾细胞（MOG-SP）的输注可显著预防和逆转 EAE。进一步的研究表明，受保护的动物在 EAE 再诱导时表现出明显延迟的 EAE。此外，从受保护的小鼠中过继转移 CD4+T 细胞至同种系 naive 小鼠，使受体小鼠对 EAE 诱导具有抗性。出乎意料的是，在体外通过 MOG35-55 刺激时，所有组中的 CD4+T 细胞增殖相似。然而，对增殖的 CD4+T 细胞的进一步分析显示，Foxp3+调节性 T 细胞（MOG-SP 组中为 70%，而对照组中为 10-25%）和 IL-17+细胞（MOG-SP 组中为 2-3%，而对照组中为 6-9%）之间存在显著差异。此外，我们发现 MOG-SP 处理还显著减弱了 MOG35-55 反应性 IFN-γ产生 Th1 细胞。这些发现表明，MOG-SP 处理诱导 EAE 保护性 MOG35-55 特异性调节性 T 细胞，并抑制 EAE 致病性 Th17 和 Th1 细胞。我们的研究为基于抗原的 EAE 免疫疗法提供了一种新方法，该方法有可能转化为多发性硬化症的免疫治疗的临床应用。
