可溶性髓鞘少突胶质细胞糖蛋白(MOG)诱导实验性自身免疫性脑脊髓炎(EAE)小鼠免疫耐受的机制

Mechanism of immune tolerance induced by soluble myelin oligodendrocyte glycoprotein in mice with experimental autoimmune encephalomyelitis

目的探讨可溶性髓鞘少突胶质细胞糖蛋白(MOG)诱导实验性自身免疫性脑脊髓炎(EAE)小鼠免疫耐受的机制。方法将EAE小鼠随机分为MOG肽治疗组、卵清蛋白(OVA)处理组和对照组,分别于EAE诱导的第6～16天腹腔注射MOG肽、OVA肽和同等剂量的PBS,通过比较各组小鼠临床评分,脾脏(SP)大小,脾脏和中枢神经系统(CNS)的脑和脊髓浸润淋巴细胞数,流式细胞术分析T细胞表型及其功能,探讨T细胞迁移在可溶性MOG肽诱导的EAE免疫耐受中的作用;流式细胞术分析脾脏、CNS浸润CD11b+抗原提呈细胞(APC)的成熟,免疫荧光技术分析成熟APC与效应性CD4+T细胞的相互作用,研究成熟APC在T细胞迁移中的作用。结果腹腔注射可溶性MOG肽可抑制脾脏内的效应性T细胞向CNS迁移,并诱导脾脏APC成熟,抑制CNS浸润APC成熟;MOG肽诱导的成熟APC可与MOG反应性CD4+T细胞相互作用并聚集在一起,进而抑制效应性T细胞的迁移。结论可溶性MOG肽通过诱导脾脏APC成熟,成熟APC与MOG-T细胞相互作用,抑制脾脏MOG-T细胞向CNS迁移,诱导EAE免疫耐受。

Objective To explore the mechanism of immune tolerance induced by soluble MOG35-55（ MOG） peptide in mice with experimental autoimmune encephalomyelitis（ EAE）. Methods EAE mice were randomly divided into three groups,MOG, OVA and control groups, which were injected intraperitoneally with MOG, OVA peptide and PBS,respectively,from day 6 to day 16 after EAE induction. Lymphocytes in the spleen and CNS were enumerated and their phenotypes and function were analyzed by flow cytometry to explore the role of T cell migration in MOG-induced EAE tolerance. Next,CD11 b＋antigen presenting cells（ APCs） in the spleen and CNS infiltration were analyzed by flow cytometry to evaluate their maturation,and the role of mature APCs in blocking MOG-CD4＋T cells trafficking to CNS was determined by immunofluorescence technique. Results MOG trapped effector T cells in the spleen and protected mice from EAE. MOG triggered the maturation of splenic APCs,while prevented the maturation of CNS-infiltrating APCs. MOG-loaded APCs could interact with MOG reactive CD4＋T cells and limit their migration. Conclusion MOG can protect mice from EAE by inducing the maturation of splenic APCs that interact with MOG-T cells and trap them in the periphery.