B7H1-Ig诱导Tr1细胞向CD4^+CD25^+Foxp3^+Treg细胞转化的研究  

B7H1-Ig-initiated Tr1 cells transform into CD4^+CD25^+Foxp3^+Tregs in vitro

作　　者：邵晓轶[1,2] 马妍慧[2] 路丽明[2] 周芸[2] 杨志强[2] 顾鹏[2] 李佐青[2] 周光炎[2] 

机构地区：[1]南通大学医学院免疫学系,南通226001 [2]上海交通大学医学院,上海市免疫学研究所,上海200025

出　　处：《现代免疫学》2012年第6期441-449,共9页Current Immunology

基　　金：国家自然科学基金资助项目(30772018;30972691;30700766);上海市人才计划项目(10QA1405900;XYQ2011015);江苏高校优势学科建设工程资助项目;南通市科技计划项目(BK2011019)

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。To investigate the transfomation and relationship between type 1 regulatory T cells（Trl） and CD4^＋ CD25^＋ Foxp3^＋Tregs, isolated naive CD4^＋ CD62L^＋ T cells were stimulated with plate-bound B7HI-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-13 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 B7Hl-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 B7HI-Ig can induce the generation of Trl cells. It was also found that TGF-β had no effect on the differentiation of BTHl-Ig-stimulated naive CD4^＋ T cells, but it could promote the B7Hl-stimulated, fully differentiated Trl cells to transform into CD4^＋ CD25^＋ Foxp3^＋ Tregs. These findings strongly suggest that Trl 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.

关 键 词：B7H1 调节性T细胞 TGF-Β 免疫抑制 

分 类 号：R392.12[医药卫生—免疫学]