【摘要】 为探讨Ⅰ型调节性T细胞(Tr1)与CD4+CD25+Foxp3+Treg之间的转化和相互关系,以预包被而固相化的B7H1-Ig融合蛋白加抗CD3单抗刺激初始CD4+CD62L+T细胞,分析细胞因子及Foxp3表达水平的变化,检测细胞功能;在B7H1-Ig开始刺激时或诱导细胞分化结束后加入重组人TGF-β,观察其对细胞分化的影响。结果显示,B7H1-Ig激活的CD4+T细胞产生高水平IL-10、IFN-γ和IL-5,极低水平的IL-2和IL-4,不表达Foxp3,通过分泌抑制性细胞因子IL-10发挥免疫抑制功能,证实B7H1-Ig可诱导Tr1细胞的产生。同时发现TGF-β不影响B7H1-Ig刺激的初始CD4+T的分化,却可促进B7H1-Ig诱导的已分化Tr1细胞向CD4+CD25+Foxp3+Treg转化,提示在特定条件下,Tr1细胞可转化的CD4+CD25+Foxp3+Treg。研究结果为将来临床应用CD4+Treg治疗免疫失调性疾病奠定了基础。更多还原

【Abstract】 To investigate the transfomation and relationship between type 1 regulatory T cells(Tr1) and CD4+CD25+Foxp3+Tregs,isolated nave CD4+CD62L+T cells were stimulated with plate-bound B7H1-Ig plus anti-CD3,then the expression levels of cytokines and Foxp3 were analyzed,and the function of the resulting T cells were detected.Recombinant human(rh)TGF-β was added at the time of culture initation or after stimulation to observe how it affected the differentiation of CD4+T cells in the culture.Our results showed that B7H1-Ig-activated CD4+T cells had the following characteristics: They produced high levels of IL-10,IFN-γ and IL-5 and a very low level of IL-2 and IL-4.They didn’t express the transcription factor Foxp3,but played immunosuppressive roles by secreting IL-10.These results demonstrate that B7H1-Ig can induce the generation of Tr1 cells.It was also found that TGF-β had no effect on the differentiation of B7H1-Ig-stimulated nave CD4+T cells,but it could promote the B7H1-stimulated,fully differentiated Tr1 cells to transform into CD4+CD25+Foxp3+Tregs.These findings strongly suggest that Tr1 cells can transform into CD4+CD25+Foxp3+Treg cells under certain conditions.Our study might be helpful to facilitate the using of CD4+Treg for treatment of diseases caused by immunological disregulation.更多还原