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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。
To explore the transformation and correlation between type I regulatory T cells (Tr1) and CD4 + CD25 + Foxp3 + Tregs, pre-coated and immobilized B7H1-Ig fusion protein plus anti-CD3 mAb was used to stimulate naive CD4 + CD62L + T cells. The changes of cytokines and Foxp3 expression were analyzed to detect the cell function. The recombinant human TGF-β was added when B7H1-Ig began to be stimulated or induced to differentiate, and the effect on cell differentiation was observed. The results showed that B7H1-Ig-activated CD4 + T cells produced high levels of IL-10, IFN-γ and IL-5, very low levels of IL-2 and IL-4, did not express Foxp3, secreted inhibitory cytokines IL -10 play immunosuppressive function, confirmed that B7H1-Ig can induce Tr1 cell production. At the same time, it was found that TGF-β did not affect the differentiation of primary CD4 + T stimulated by B7H1-Ig, but promoted the transformation of differentiated Tr1 cells induced by B7H1-Ig into CD4 + CD25 + Foxp3 + Tregs, suggesting that under certain conditions, Transformed CD4 + CD25 + Foxp3 + Tregs. The results laid the foundation for the clinical application of CD4 + Treg in the treatment of immune disorders.