1型糖尿病患者骨髓间质干细胞对CD4^+Foxp3^+T细胞水平的影响

The effect of bone marrow mesenchymal stem cells from type 1 diabetes patients on CD4^+ Foxp3^+ regulatory T cell

目的:探讨骨髓间质干细胞(MSC)体外对1型糖尿病(T1DM)患者外周血CD4+Foxp3+T细胞水平的影响方法:T1DM患者外周血单个核细胞(PBMC)分别与T1DM患者和正常人骨髓MSC按不同比例体外共培养72 h,检测共培养后PBMC中CD4+Foxp3+T细胞百分率。结果:正常骨髓MSC与T1DM患者PBMC共培养后CD4+Foxp3+T细胞百分率显著升高(P<0.05),且存在剂量依赖性,T1DM MSC也可上调T1DM患者CD4+Foxp3+T细胞水平,但作用较正常MSC弱(P<0.05);正常MSC培养上清也可上调T1DM患者PBMC中CD4+Foxp3+T细胞水平,但作用弱于MSC∶PBMC=1∶1组(P<0.05)。结论:T1DM患者MSC上调CD4+Foxp3+T细胞百分率低于正常人MSC可能是T1DM患者发病的因素之一。

Objective： To investigate the in vitro immune regulatory effects of bone-marrow mesenchymal stem cells（MSC） on CD4＋ Foxp3＋ T cells in peripheral blood of patients with type 1 diabetes.Methods： Human MSC were isolated and expanded from bone marrow cells of related healthy donors and T1DM patients.The percentages of CD4＋ Foxp3＋ T cells in peripheral blood were detected by flow cytometry.Human peripheral blood mononuclear cells（PBMC） were prepared by centrifugation on a Ficoll Hypaque density gradient.The MSC and PBMC from unrelated donors（MSC∶PBMC =1∶1,1∶10,1∶50） were added into 24-well plates.After 72 h of co-culture,the percentages of CD4＋ Foxp3＋ T cells were detected by flow cytometry.Results： The co-culture of normal bone marrow MSC with PBMC from T1DM patients resulted in a statistically significant increase of CD4＋ Foxp3＋ T cells percentage in PBMC on a dose dependent（P0.05）.The percentages of CD4＋ Foxp3＋ T cells of PBMC from T1DM patients co-cultured with T1DM MSC were lower than that with normal MSC（P0.05）.The cultured supernatant of normal MSC also upregulated the percentages of CD4＋ Foxp3＋ T cells of PBMC from T1DM patients（P0.05）.Conclusion： Abnormal ability of upregulation of Treg population of T1DM MSC may be one of the mechanisms of T1DM development.