间充质干细胞分泌TGF-β1抑制异体T细胞反应性

为探讨骨髓间充质干细胞（MSC）诱导异体T细胞反应性下降的机制。应用流式细胞术检测了异体T细胞与骨髓间充质干细胞共培养前后CD4，CD8，CD25和CD28等的变化，同时应用RT-PCR测定MSC是否表达IL-4，IFN-γ和TGF-β1等细胞因子，并用ELISA的方法验证培养上清中蛋白的存在。结果显示，异体T细胞与MSC共培养后，CD8^ 细胞增多，CD25^ 细胞减少，RT-PCR检测结果证明MSC高表达TGF-β1基因，但不表达IL-4和IFN-γ基因，ELISA证实MSC培养上清存在TGF-β1蛋白，其72小时分泌量约为1ng/ml。结论：骨髓MSC在体外可使异体T细胞对异体抗原的反应性减低，这种作用体现在细胞亚群的改变与MSC分泌TGF-β1有关，这一研究结果为预防HLA不相同合骨髓移植中GVHD的发生提出一条新的思路。

Mesenchymal Stem Cells Suppress Allogeneic T Cell Responses by Secretion of TGF-β1

To investigate the mechanisms underlying the issue that bone marrow mesenchymal stem cells (MSC) could trigger low responsiveness of allogeneic T lymphocytes against alloantigens,phenotypes of T cells were analysed with flow cytometry before and after co-culture of allogeneic T lymphocytes with MSC.Further,expression of cytokines,including IL-4,IFN-7 and TGF-fil,was evaluated by RT-PCR and ELISA as well.The results showed that CD8+ subpopulation was increased and CD25+ subset was decreased in proportion after co-culture of allogeneic T lymphocytes with MSC for 2 weeks.RT-PCR assay showed that MSC expressed TGF-fil but not IL-4 and IFN-y,and the result was further proved by ELISA assay showing that the secretion of TGF-fil reached to 1 ng/ml in 72 hours.It was concluded that allogeneic MSC suppressed T cells activation by alteration of T cell subpopulations.The suppressive effect was at least in part due to the secretion of TGF-fil.The results indicate that MSC pretreatment might be useful in the prevention of GVHD in HLA-mismatched bone marrow transplantation and further,donors for hematopoietic stem cells could be selected from greater potentials.