骨髓基质干细胞对过继免疫实验性自身免疫性脑脊髓炎的影响及免疫调节机制

Treatment of adoptive transfer experimental autoimmune encephalomyelitis by bone marrow stromal cells and its immunomodulation mechanism

目的探讨骨髓基质干细胞(BMSCs)对过继免疫实验性自身免疫性脑脊髓炎(AT-EAE)的治疗作用及相关免疫调节机制。方法分离纯化培养BMSCs,建立EAE动物模型,在EAE动物模型发病高峰期取淋巴细胞,加入MBP刺激并与BMSCs共培养,并设未共培养的单纯MBP刺激对照组。将培养后的淋巴细胞对大鼠进行过继免疫回输,通过体外增殖实验,流式细胞仪检测以及体内临床评分评估BMSCs对EAE的治疗作用及其机制。结果BMSCs共培养MBP组与MBP组相比,淋巴细胞增殖明显被抑制,CD4+Foxp3+细胞显著增高而CD4+IL-17+细胞显著降低,培养后的淋巴细胞进行过继免疫回输后,干细胞共培养组临床评分显著降低(P<0.05)。结论BMSCs通过调节免疫系统的调节性T细胞(Treg)和Th17的细胞平衡,即上调调节性T细胞分化和下调Th17细胞功能,对EAE起治疗作用。

Objective To investigate therapeutic effect and immunomodulation mechanism of bone marrow stem cells（BMSCs） treating adoptive transfer experimental autoimmune encephalomyelitis（AT-EAE）.Methods BMSCs were purified and cultured,EAE model was established,T lymphocytes were isolated at the peak of disease.T cells were stimulated with MBP in the presence or absence of BMSCs,these cells were injected into the naive rat tail vein.The corresponding indexes of EAE were evaluated by lymphocyte proliferation assays and flow cytometry test in vitro,clinical assessment in vivo.Results Compared with MBP group,the proliferation of lymphocytes and clinical score of（BMSCs＋MBP） group significantly decreased（P0.05）.The proportion of Treg increased while Th17 decreased.Conclusion BMSCs strongly reduce proliferative responses of lymphocytes of EAE rats,promote Treg generation and inhibit Th17 cell generation.