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目的研究不成熟髓源树突状细胞(iMDC)负载Tα146-162对实验性自身免疫性重症肌无力(EAMG)的治疗作用及其机制。方法 Tα146-162负载于体外培养的iMDC,获得Tα146-162-iMDC。20只 EAMG评分1～2分的C57BL/6小鼠随机分为治疗组和对照组。治疗组第0、7、14天皮下注射Tα146-162- iMDC,对照组则皮下注射1 ml PBS。对EAMG小鼠进行肌力评分,入组后第21天结束观察。~3H-TDR掺入法检测淋巴细胞增殖反应,ELISA法检测淋巴细胞培养液上清中IFN-γ、IL-6、TGF-β的含量。结果与对照组相比,治疗组平均临床评分和抗原特异性淋巴细胞增殖反应显著降低(P<0．01),淋巴细胞抗原特异性IFN-γ、IL-6分泌显著减少(P<0．01),TGF-β的分泌两组差异无统计学意义。结论Tα146-162-iMDC 能改善EAMG发病小鼠的临床表现,其诱导免疫耐受可能与抗原特异性的抑制淋巴细胞增殖和IFN-γ、 IL-6的分泌有关,TGF-β在耐受诱导中可能不发挥主要作用。
Objective To investigate the therapeutic effect and mechanism of Tα146-162 on experimental autoimmune myasthenia gravis (EAMG) in immature myelogenous dendritic cells (iMDC). Method Tα146-162 was loaded on iMDC cultured in vitro to obtain Tα146-162-iMDC. Twenty C57BL / 6 mice with 1 to 2 EAMG scores were randomly divided into treatment group and control group. Tα146-162-iMDC was injected subcutaneously in the treatment group on days 0, 7 and 14, while in the control group, 1 ml PBS was injected subcutaneously. Muscle power was scored on EAMG mice and observed on the 21st day after enrollment. The 3H-TDR incorporation method was used to detect the proliferation of lymphocytes, and the levels of IFN-γ, IL-6 and TGF-β in the supernatant of lymphocyte culture medium were detected by ELISA. Results Compared with the control group, the mean clinical scores and antigen-specific lymphocyte proliferation responses in the treatment group were significantly decreased (P <0.01), and the levels of lymphocyte antigen-specific IFN-γ and IL-6 secretion were significantly decreased (P <0. 01), TGF-β secretion was no significant difference between the two groups. Conclusion Tα146-162-iMDC can improve the clinical manifestations in mice with EAMG. The induced immune tolerance may be related to the antigen-specific inhibition of lymphocyte proliferation and the secretion of IFN-γ and IL-6. The induction of tolerance of TGF- May not play a major role.