多发性骨髓瘤患者间充质干细胞对T细胞及树突状细胞作用的初步研究  

Inhibitation of T cells and dendritic cells by mesenchymai stem cells derived from the bone marrow of multiple myeloma patients

作　　者：王国蓉[1] 张晓伟[2] 李静[3] 陈文明[1] 

机构地区：[1]首都医科大学附属北京朝阳医院血液科北京市多发性骨髓瘤临床研究中心, 100020 [2]中国民航总医院内科 [3]北京丰台医院内科

出　　处：《白血病．淋巴瘤》2010年第12期710-713,共4页Journal of Leukemia & Lymphoma

基　　金：基金项目：国家自然科学基金（30872982）;北京市自然科学基金（7082036）

摘　　要：目的 探讨多发性骨髓瘤（MM）患者与健康供者骨髓来源的间充质干细胞（MSC）对T细胞及树突状细胞（DC）功能的影响.方法 从MM患者及健康志愿者骨髓获得MSC（MM-MSC或ND-MSC）,ELISA检测细胞因子水平,流式细胞术检测细胞表面标记,Annexin V-FITC/PI检测凋亡.两组MSC分别加入DC、T细胞及U266细胞共培养体系中,比较MSC对DC介导的T细胞杀伤功能的影响.结果 MM-MSC比ND-MSC分泌转化生长因子-1（TGF-1）水平更高（P＜0.05）.MM-MSC具有更强的抑制T细胞增殖活化和杀伤功能以及促进T细胞凋亡的能力（P＜0.05）.MSC与DC共培养时,能显著抑制DC成熟分化,并显著减少DC细胞白细胞介素-12分泌（P＜0.01）.DC与T细胞及U266细胞共培养时,加入MSC后,U266细胞凋亡明显减少（P＜0.01）,MM-MSC的抑制作用更强（P＜0.01）.结论 与ND-MSC比较,MM-MSC表达TGF-1较高,对DC的分化、成熟和细胞因子分泌及对T细胞活化及肿瘤细胞杀伤作用的抑制更强,并可明显抑制DC辅助T细胞对U266细胞的杀伤作用.骨髓微环境中MSC可能在MM发病机制中起重要作用.Objective To investigate the effects of mesenchymal stem cells （MSC） derived from bone marrow of multiple myeloma patients （MM-MSC） and normal donors （ND-MSC） on the function of T cells and dendritic cells （DC）. Methods MSC were isolated and cultured from bone marrow of multiple myeloma patients and normal donors. Cytokines were detected by enzyme-linked immunosorbent assay （ELISA）.Immunophenotype was detected by flow cytometry （FCM）. The apoptosis of cells were detected by Annexin-V/PI assay. In order to compare the influence of MSC （MM-MSC group vs ND-MSC group） on DC-mediated T cells killing function, ND-MSC （ND-MSC group） and MM-MSC （MM-MSC group） were co-cultured with DC ＋T cells ＋ U266 cells, respectively. Results The expression of TGF-1 by MM-MSC were higher than that by ND-MSC （P 〈0.05）. The proliferation of T lymphocytes, activation and killing function were significantly inhibited and T cells apoptosis were significantly promoted by MM-MSC than that by ND-MSC （P 〈0.05）.When co-cultured with DC, MSC inhibited immature DC （imDC） maturation and IL-12 expression （P 〈0.01）.After MSC co-cultured with DC ＋ T cells ＋ U266 cells, the apoptosis of U266 cells induced by T cells decreased significantly and the apoptosis were significantly inhibited by MM-MSC than by ND-MSC （P 〈0.01）.Conclusion MM-MSC can inhibit T cell activation and killing function and express a high level TGF-1.MM-MSC may inhibit DC differentiation, maturation and cytokine secretion. MSC in bone marrow microenvironment may play an important role in pathogenesis of MM.

关 键 词：多发性骨髓瘤 间充质干细胞 树突细胞 免疫抑制 

分 类 号：R733[医药卫生—肿瘤]