目的探讨多发性骨髓瘤(MM)患者的骨髓间充质干细胞(MSC)的免疫原性及其调控免疫的功能和机制。方法获取MM患者的骨髓MSC,在低血清培养液中培养和扩增。流式细胞仪检测免疫表型;酶联免疫吸附试验检测MSC培养上清液中细胞因子的分泌水平;混合淋巴细胞反应检测骨髓MSC抑制异体T淋巴细胞增殖的能力;流式细胞仪检测MSC对树突状细胞(DC)吞噬功能的影响;混合淋巴细胞反应检测MM骨髓MSC抑制DC介导的异体T淋巴细胞增殖能力。结果MM患者的MSC不表达HLA-DR和共刺激分子CD80、CD83、CD86和CD40。MM患者的MSC通过分泌转化生长因子β1(TGF-β1)和肝细胞生长因子(HGF)抑制异体T淋巴细胞的增殖。MM患者的MSC具有抑制DC吞噬作用的功能;MM骨髓MSC抑制DC分泌白细胞介素12(IL-12),并可以抑制DC介导的异体T淋巴细胞增殖。结论MM骨髓MSC具有低免疫原性及体外调节免疫的功能,该免疫调节功能与其分泌细胞因子有关。
Objective To study the immunogenicity, immune modulatory effects and mechanisms of mesenthymal stem cells (MSCs) derived from the bone marrow of patients with multiple myeloma (MM). Methods The mononuclear cells from the bone marrow of MM patients were obtained and cultured. Immunophenotypes were investigated by using FACS. The levels of cytokines were determined by using enzyme linked immunosorbant assay (ELISA). The endocytosis of monocyte-derived dendritic cells (DCs) was investigated by using FACS. Moreover, the immunoregulatory ability of DCs on proliferation of T lymphocytes was detected by using mixed lymphocyte culture assay. Results MM-derived MSCs had no expression of HLA-DR and co-stirnulatory molecules (CIN0, CD80, CD83 and CD86). MM-derived MSCs could significantly suppress proliferation of T lymphocytes in a dose-dependent manner, which could be reversed by anti- TGF-β1 and anti-HGF antibodies. MM-derived MSCs inhibit the endocytosis of DCs. MM-derived MSCs could inhibit the secretion of IL-12 and significantly inhibit the function of DCs on proliferation of T lymphocytes. Conclusion MM-derived MSCs harbored low immunogenicity and immunoregulatory effect in vitro, and this effect was achieved through eytokines.