激发型CD40单克隆抗体对实验性自身免疫性重症肌无力耐受的影响

目的 探讨激发型CD40单克隆抗体(CD40mAb)对未成熟树突状细胞(iDC)诱导实验性自身免疫性重症肌无力(EAMG)耐受的影响. 方法 20只Lewis大鼠按照随机数字表法分为正常组、EAMG对照组、耐受组和CD40mAb组,每组5只.耐受组和CD40mAb组每只大鼠于背部皮下分4点分别注射总量为1 mL的乙酰胆碱受体(AChR)+iDC,其中CD40mAb组每只大鼠在接种iDC的同时和次日分别给予CD40mAb腹腔注射,0.5mg/次.EAMG对照组注射1 mL无血清培养基.正常组不做任何处理.3周后用AChR和完全弗氏佐剂(CFA)免疫,观察免疫7周后重症肌无力(MG)相关指标的改变. 结果 耐受组大鼠和正常组大鼠一样,用AChR和CFA免疫后,MG相关指标无明显改变;而CD40mAb组大鼠和EAMG对照组一样,产生了明显的MG症状,重复电刺激出现明显衰减,血清AChRab滴度明显增高,神经肌肉接头呈现典型的MG样改变. 结论 激发型CD40mAb可阻止AChR负载的iDC诱导EAMG耐受,提示iDC功能异常可能与MG异常免疫反应的启动密切相关.

Abstract：

Objective To investigate the effect of agonist CD40 monoclonal antibody (CD40mAb) on the tolerance of experimental autoimmune myasthenia gravis (EAMG) induced by immature dendritic cells (iDCs). Methods Lewis rats were equally randomized into normal group,EAMG group, tolerance group and CD40mAb treatment group (n=5). Rats in the tolerance group and CD40mAb treatment group were vaccinated with AChR pulsed iDCs; and rats in the CD40mAb treatment group were intraperitoneally injected CD40mAb at a dosage of 0.5 mg once when performing the vaccination and on the 2rd d of vaccination. One mL serum-free medium was given to the rats in the EAMG group; normal group did not receive any treatment. Three weeks after that, rats in the above 4 groups were immunized with AChR and complete Freund's adjuvant (CFA). Seven weeks after the immunization, the corresponding indexes of MG were observed: behavioral assessment was performed and electromyogram was employed to detect the repetitive nerve stimulation on these rats; enzyme-linked immunosorbent assay (ELISA) was used to determine the level of AChRab; the pathological changes of neuromuscular junction were also detected. Results Just as the rats in the normal group, the rats in the tolerance group did not have significant changes in any of the corresponding indexes of MG after being immunized with AChR and CFA. In contrast, rats in both EAMG group and CD40mAb treatment group showed typical changes in the corresponding indexes of MG: their electromyogram wave amplitude obviously attenuated; the level of serum AChRab increased and neuromuscular junction appeared as a typical damage of MG. Conclusion Agonist CD40mAb could abrogate the tolerance of EAMG induced by AChR pulsed iDCs, suggesting that the dysfunction of DCs is related to the priming of abnormal immune of MG.

Effect of agonist CD40 monoclonal antibody on the tolerance of experimental autoimmune myasthenia gravis

Objective To investigate the effect of agonist CD40 monoclonal antibody (CD40mAb) on the tolerance of experimental autoimmune myasthenia gravis (EAMG) induced by immature dendritic cells (iDCs). Methods Lewis rats were equally randomized into normal group,EAMG group, tolerance group and CD40mAb treatment group (n=5). Rats in the tolerance group and CD40mAb treatment group were vaccinated with AChR pulsed iDCs; and rats in the CD40mAb treatment group were intraperitoneally injected CD40mAb at a dosage of 0.5 mg once when performing the vaccination and on the 2rd d of vaccination. One mL serum-free medium was given to the rats in the EAMG group; normal group did not receive any treatment. Three weeks after that, rats in the above 4 groups were immunized with AChR and complete Freund's adjuvant (CFA). Seven weeks after the immunization, the corresponding indexes of MG were observed: behavioral assessment was performed and electromyogram was employed to detect the repetitive nerve stimulation on these rats; enzyme-linked immunosorbent assay (ELISA) was used to determine the level of AChRab; the pathological changes of neuromuscular junction were also detected. Results Just as the rats in the normal group, the rats in the tolerance group did not have significant changes in any of the corresponding indexes of MG after being immunized with AChR and CFA. In contrast, rats in both EAMG group and CD40mAb treatment group showed typical changes in the corresponding indexes of MG: their electromyogram wave amplitude obviously attenuated; the level of serum AChRab increased and neuromuscular junction appeared as a typical damage of MG. Conclusion Agonist CD40mAb could abrogate the tolerance of EAMG induced by AChR pulsed iDCs, suggesting that the dysfunction of DCs is related to the priming of abnormal immune of MG.