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目的 探讨未成熟树突状细胞(iDC)对实验性自身免疫性重症肌无力(EAMG)的影响。方法 用小剂量粒 巨噬细胞集落刺激因子(GM -CSF)体外诱导骨髓前体细胞,获得的iDC用乙酰胆碱受体(AChR)负载后皮下接种同基因大鼠,3周后通过体外试验观察脾细胞对AChR的增殖反应,同时用AChR和完全弗氏佐剂(CFA)免疫大鼠,观察免疫-7周后MG相关指标的改变。结果 小剂量GM -CSF诱导所获得的iDC与成熟DC(mDC)相比,其表面MHCⅡ和共刺激分子CD80、CD86的表达低,摄取dextran -FITC的能力强但刺激同种T细胞增殖的能力弱。接种iDC、mDC、AChR负载的mDC的大鼠和对照组一样,体外脾细胞对AChR的刺激均强烈增殖,用AChR和CFA免疫后,产生明显的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;而接种AChR负载的iDC的大鼠脾细胞对AChR的刺激呈现明显的增殖抑制但对卵清蛋白的刺激仍强烈增殖,MG相关指标均未见明显改变。结论 骨髓前体细胞经小剂量GM -CSF诱导产生了iDC ,AChR负载的iDC可诱导EAMG耐受。
Objective To investigate the effect of immature dendritic cells (iDCs) on experimental autoimmune myasthenia gravis (EAMG). Methods Bone marrow progenitor cells were induced in vitro by low dose of granulocyte-macrophage colony-stimulating factor (GM-CSF). The obtained iDC was inoculated subcutaneously with acetylcholine receptor (AChR) and inoculated three weeks later. Cells were stimulated with AChR and immunized with AChR and complete Freund’s adjuvant (CFA). The changes of MG-related markers after 7 weeks of immunization were observed. Results The iDC obtained with low dose of GM-CSF showed low expression of MHC II and co-stimulatory molecules CD80 and CD86 compared with mature DCs (mDCs), the ability to ingest dextran-FITC but the ability to stimulate allo-T cell proliferation weak. Inoculated with iDC, mDC, AChR loaded mDC rats and control group, in vitro splenocytes stimulated AChR were strongly proliferated with AChR and CFA immunized, produce significant MG symptoms, repeated electrical stimulation showed a significant decline in serum AChRAb The titers of the neurons were significantly increased and the typical MG-like changes were observed in the neuromuscular junctions. However, splenocytes from AChR-loaded iDC showed a significant inhibition of AChR stimulation but still strongly stimulated the ovalbumin. MG-related indicators No significant change. Conclusion Bone marrow progenitor cells induced iDC by low dose of GM-CSF and AChR-loaded iDC induced EAMG tolerance.