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骨髓间充质干细胞对外周血T淋巴细胞亚群影响的体外实验研究

Study on the ex vivo effect of mesenchymal stem cells on peripheral subsets of T lymphocyte

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【作者】 宣旻谢晓宝邱国强余亚萍吴浩清王志林

【Author】 XUAN Min XIE Xiaobao QIU Guoqiang YU Yaping WU Haoqing WANG Zhilin (Department of Hematology, The Third Affiliated Hospital, Soochow University, Changzhou 213003, China)

【机构】 常州市第一人民医院血液科常州市第一人民医院血液科 (江苏常州213003)(江苏常州213003)

【摘要】 目的:探讨骨髓间充质干细胞(MSC)在体外对T淋巴细胞亚群及其分泌的细胞内因子的影响。方法:通过Ficoll-Hypaque梯度密度离心法分离出正常人骨髓单个核细胞,体外培养扩增MSC,获取第3代细胞。将其按照不同的比例加入双向混合淋巴细胞培养(MLC)体系中,在第1,3,5天,采用MTT比色法检测各组MLC中的T淋巴细胞的增殖情况,再用流式细胞术分析各组T细胞亚群及其内因子白介素(IL)-4和干扰素(IFN)-γ的分泌变化情况。结果:加入了MSC的MLC体系中,MSC对T淋巴细胞的增殖抑制具有剂量依赖性,且随着时间延长,抑制程度增强;其中,CD4+T细胞亚群受抑不如CD8+T细胞亚群显著;而根据T细胞内因子的变化,Th1和Tc1的比率较对照组有显著降低,而Th2和Tc2的比率却有轻度上升。结论:MSC在体外能够明显抑制T淋巴细胞的增殖,尤其是CD8+T细胞(CTL)。除此之外,它还能降低MLC体系中的Th1和Tc1,升高Th2和Tc2。所以在临床上可能有减轻移植后急性移植物抗宿主病(aGVHD)的发生,而保留移植物抗白血病(GVL)的潜力。

【Abstract】 Objective:To investigate the effect of mesenchymal stem cell (MSC) on cytokines and subsets of T lymphocyte in vitro. Method: Normal human bone marrow mononuclear cells were isolated by Ficoll-Hypaque density gradient, ex vivo MSCs were culture-expanded, obtained after the third passage. The MSC were added to the two-way mixed lymphocyte culture (MLC) according to different proportion. On day 1, 3 and 5, the proliferation of T lymphocytes of each group of MLC-MSC and ctrl-MLC was measure with MTT coloremetry. The subsets and Cytokines of T lymphocytes were analyzed by flow cytomety before and on 3th day after co-culture of MLC with MSC. Result:MLC added MSC induce dose-dependent inhibition of T lymphocytes proliferation, and more effectively in company with co-culture time; CD4+ T cell subsets was not suppressed as obviously as CD8+ T cell subsets; Th1 and Tc1 decrease significantly than control cultures without MSC. But Th2 and Tc2 slightly increased in all experiments. Conclusion: MSC can significantly suppress T-lymphocyte proliferation, especially CD8+ T cell subsets, Otherwise it can decrease activated Th1 and Tc1, increase Th2 and Tc2. MSC have potential of alleviating acute graft-versus-host disease(aGVHD) and maintaining graft versus leukemia (GVL).

  • 【文献出处】 临床血液学杂志 ,Journal of Clinical Hematology , 编辑部邮箱 ,2007年03期
  • 【分类号】R392
  • 【被引频次】1
  • 【下载频次】87
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