TGF-β1诱导CD4^+CD25^-T细胞分化为CD4^+CD25^+调节性T细胞  

TGF-β1 induces differentiation of CD4^+CD25^-T cells into CD4^+CD25^+ reg ulatory T cells

作　　者：袁劲[1] 吴轲[1] 徐逸[1] 曾宁[1] 陈忠华 

机构地区：[1]华中科技大学同济医学院同济医院器官移植研究所教育部卫生部重点实验室,武汉430030

出　　处：《免疫学杂志》2007年第6期589-592,597,共5页Immunological Journal

基　　金：国家自然科学基金资助项目(30671989)

摘　　要：目的研究TGF-β1诱导CD4+CD25+调节性T细胞分化的能力及其相关机理。方法①利用丝裂霉素处理的Balb/C裸鼠脾细胞(同种抗原)刺激C57BL/6小鼠T细胞,同时给予TGF-β1予以干预(按TGF-β1剂量不同设立4组:对照组,低浓度组,中浓度组和高浓度组),共同培养5天后,用流式细胞仪检测CD4+CD25+T细胞比例;同时用RT-PCR检测培养细胞中Foxp3的表达水平。②在第一部分实验基础上,通过MACS分离获取C57BL/6小鼠CD4+CD25-T细胞,用同种抗原刺激后,给予TGF-β1干预,培养5d后分离CD4+CD25+T细胞,利用混合淋巴细胞培养系统检测其抑制淋巴细胞增殖的能力。结果T细胞经同种抗原刺激后,在中、高浓度TGF-β1诱导下CD4+CD25+T细胞比例均明显升高,Foxp3的表达水平也相应增加,与对照组相比有显著性差异(P<0.05)。TGF-β1可直接诱导CD4+CD25-T细胞转化为CD4+CD25+T细胞,转化后的CD4+CD25+T细胞可有效抑制淋巴细胞增殖。结论TGF-β1可诱导CD4+CD25-T细胞转化为CD4+CD25+Treg,促进其表达Foxp3,并能够抑制淋巴细胞增殖。Objective To investigate the capability of TGF-β1 to induce the differentiation of CD4^＋ CD25^＋ regulatory T cells and the mechanisms. Metheds The nude Balb/c splenocytes pretreated with mitomycin as the stimulator were added to C57BL/6 T cells with or without TGF-β1 for a 6-day culture. Four groups were established： control group （0 ng/mL TGF-β1）, low concentration group （0.1 ng/mL）, middie concentration group （5 ng/mL）, and high concentration group （ 10 ng/mL）. At the end-point of culture, the percent of CD4^＋ CD25^＋ T cells and the expression of Foxp3 mRNA were measured by FACS and RT-PCR, individually. Then CD4^＋ CD25^- T cells were isolated by MACS and stimulated with alloantigen and TGF-β1. After a 6-day culture, CD4^＋ CD25^＋ T cells were isolated and we measured the immunosuppressive activity of these cells. Results The 5 ng/mL and 10 ng/mL TGF-β1 could increase the percent of CD4^＋ CD25^＋ T cell and the expression of Foxp3 mRNA in T cells stimulated by alloantigen （ P 〈 0.05）. TGF-β1 induced CD4^＋ CD25^- T cells to convert to CD4^＋ CD25^＋ T cells which could suppress the proliferation of lymphocytes. Condusion TGF-β1 induces CD4^＋ CD25^＋ regulator T cells from CD4^＋ CD25^- T cells which could express Foxp3 and suppress the proliferation of lymphocytes.

关 键 词：TGF-Β1 FOXP3 调节性T细胞 

分 类 号：R392[医药卫生—免疫学]