TGF-β1在早孕妇女外周血和蜕膜组织中诱导生成T调节性(Treg)细胞

目的:研究TGF-β1是否能在人母-胎界面诱导生成T调节性(Treg)细胞。方法:早孕妇女外周血和蜕膜CD4+CD25-T细胞中加入不同浓度的TGF-β1(0 ng/ml、2 ng/ml、5 ng/ml、10 ng/ml)分别于培养后第2日、第4日和第6日用流式细胞仪检测培养Foxp3的表达情况,随后将诱导生成的CD4+Foxp3+T细胞与CD8+T细胞混合培养,观察后者凋亡因子CD95配体(CD95L)的表达情况。结果:体外培养中,TGF-β1可诱导早孕妇女的外周血和蜕膜CD4+CD25-T细胞生成诱导性Treg细胞,随着培养时间增加而增强诱导效应,且在TGF-β1浓度为5 ng/ml时诱导功能最强;诱导生成的CD4+Foxp3+T细胞具有促进效应细胞CD8+T细胞凋亡的功能。结论:体外培养中,TGF-β1能将人外周血和蜕膜诱导生成Treg细胞,且具有免疫抑制功能,有良好的免疫治疗前景。

TGF-β1-mediated Conversion of Regulatory T Cells in Peripheral Blood and Decidua of Early Pregnant Women

Objective: To investigate whether TGF-β1-mediated conversion of Foxp3+regulatory T(Treg) cells occurred at the human feto-maternal interface,and whether induced Treg cells exhibited immunosupressive functions similar to naive CD4+CD25+Treg cells.Methods: CD4+CD25-T cells in peripheral blood and decidua were seperated from early pregnant women and were stimulated with increasing concentrations of TGF-β1(0 ng/ml;2 ng/ml;5 ng/ml;10 ng/ml),and changes in Foxp3 expression were determined by flow cytometry on the 2nd,4 th and 6th day after cell culture.Levels of responder T cell apoptosis were measured when TGF-β1-induced CD4+CD25-T cells were cocultured with CD8+T cells.Results: Foxp3 expression in TGF-β1-induced CD4+CD25-T cells increased in a time-dependent manner,reaching maximal level after 6 d in medium containing 5 ng/ml TGF-β1.TGF-β1-induced Treg cells suppressed cytotoxic effects by promoting apoptosis of CD8+T cells.Conclusion: TGF-β1 mediated the conversion of CD4+CD25-T cells into suppressive Treg cells,which may be a potential immunotherapy.