骨髓间充质干细胞在CD4＋CD25＋调节性T细胞减轻大鼠移植物抗宿主反应中的作用.DOCVIP

临床医学论文-骨髓间充质干细胞在CD4＋CD25＋调节性T细胞减轻大鼠移植物抗宿主反应中的作用 ????????????? 作者：田莹　邓宇斌　黄奕俊　那晓东　李艳　叶美红?? 【摘要】? 　　本研究探讨间充质干细胞（MSC）对GVHD的作用及其机制。建立大鼠同种异体骨髓移植模型，同时输入供者的T淋巴细胞诱导出移植物抗宿主反应，联合或不联合移植供体来源的MSC，观察受鼠的GVHD的发生情况;利用双荧光标记抗体标记受鼠脾脏和胸腺单个淋巴细胞，通过流式细胞术分析CD4＋CD25＋调节性T细胞亚群比例的变化，分析MSC的作用机制。结果显示：实验组的GVHD的发生程度减轻，存活率提高，而CD4/CD8比值在GVHD组出现不同程度的减少，CD4＋CD25＋调节性T细胞在实验组中的脾淋巴细胞和胸腺淋巴细胞的比例分别为31.55±7.58％、93.20±2.69％，在GVHD组中的比例分别为20.90±1.90％、57.17±6.79％，实验组中CD4+CD25+调节性T细胞比例比GVHD组中增多，具有显著性差异。结论：MSC能有效抑制HSC移植后致死性GVHD的发生，提高生存率，同时MSC可能通过作用于体内调节性T淋巴细胞而间接发挥了抑制GVHD的作用。 【关键词】? 骨髓间充质干细胞；造血干细胞移植；同种异体造血干细胞移植；移植物抗宿主病；CD4＋CD25＋调节性T细胞 　　AbstractThe study was purposed? to investigate the effects and mechanism of bone marrow-derived mesenchymal stem cells (MSCs) on graft-versus-host desease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The model of GVHD in rat had been established by allo-HSCT with donor derived T cells. The occurence of GVHD in recipients was observed in condition?with or without donor derived MSC co-transplantation. Effects of MSCs on GVHD were analyzed by model rat?survival rate and pathology.?Proportions of CD4+CD25+ regulatory T cells were determined?by using label spleen lymphocytes and thymocytes with double?fluorescent-labeled antibodies and牋 flow cytometry. The results showed that MSCs inhibited the lethal GVHD after HSC co-transplantation and increased the survival rate. The ratio of CD4/CD8? deceased in GVHD group in different levels, as? compared with that in the experimental group. The proportion of CD4+CD25+ regulatory T cells of spleen lymphocytes was 31.55±7.58％ and 20.90±1.90％ in experimental and GVHD groups, respectively. Similarly, the proportion of CD4+CD25+ regulatory T cells of thymocytes was 93.20±2.69％ and 57.17±6.79％in experimental and the GVHD groups, respectively. Meanwhile the proportion of CD4+CD25+ regulatory T cells was higher in experimental group than that in GVHD group. It is concluded that MSCs?may prevent the lethal GVHD after al