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

Role of Bone Marrow-derived Mesenchymal Stem Cells in Reduction of Graft-versus-Host Desease by Effecting CD4^+CD25^+ Regulatory T Cells in Rats

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。

The 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 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 allo-HSC co-transplantation and raise the survival rate of model rats by acting on the CD4^＋CD25^＋ regulatory T cells in vivo.