早孕期蜕膜基质细胞对蜕膜辅助性T细胞的调节作用  

Regulation of decidual stromal cells on decidual CD4^+T helper cells in early pregnancy

作　　者：刘英华[1] 韩慕天 李红[1] 王馥新[1] 刘振兴 邹琴燕[1] 朱蕊 LIU Ying-hua;HAN Mu-tian;LI Hong;WANG Fu-xin;LIU Zhen-xing;ZOU Qin-yan;ZHU Rui(The Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital,Center for Reproduction and Genetics,Suzhou 215002,China)

机构地区：[1]南京医科大学附属苏州医院苏州市立医院生殖与遗传中心,苏州215002

出　　处：《现代免疫学》2018年第5期379-384,共6页Current Immunology

基　　金：国家自然科学基金青年科学基金(81401273);江苏省基础研究计划青年基金(BK20140276);江苏省"十三五"青年医学人才项目(QNRC2016244);苏州市临床医学专家团队引进项目(SZYJTD201708);江苏省医学创新团队项目(CXTDB2017013);苏州市临床医学中心项目(SZZX201505);苏州市男性生殖研究重点实验室(SZ201718)

摘　　要：为了解蜕膜基质细胞(decidual stromal cell, DSC)对Th的免疫调节作用,分离及纯化27例不明原因自然流产(unexplained miscarriage, UM)与30例正常早孕妇女的原代DSC和蜕膜CD4^+ T细胞,并建立共培养体系。在正常早孕妇女的对照下,ELISA和FCM分析UM患者DSC和蜕膜CD4^+ T细胞,发现患者中两类细胞分泌TNF-α明显增加,而IL-4、IL-10明显减少;FCM法分析发现UM患者DSC表达CD80和CD86水平上升,表达PD-L1和PD-L2水平下降;UM患者蜕膜CD4^+ T细胞表达CTLA-4和PD-1下降;共培养5d后,UM患者CD4^+ T细胞分泌的TNF-α显著上升,而IL-4明显降低。由此UM患者母-胎界面的DSC传递协同刺激信号增强、协同抑制信号减弱,诱导CD4^+ T细胞发生Th1型免疫偏倚,可能是UM的免疫致病因素之一。To investigate the immulogical regulation of decidual stromal cells（DSC）on decidual CD4^＋T helper cells,we separated and purified DSCs and decidual CD4^＋T cells from 27 women with unexplained miscarriage（UM） and 30 controls in normal pregnancy,and established the cocultrue system.We found that the secretion of TNF-αand IFN-γby T cells and DSCs of UM were dramatically increased while those of IL-4 and IL-10 were distinctly decreased as assessed by ELISA and FCM.DSCs expressed higher levels of CD80 and CD86 but lower levels of PD-L1 and PD-L2 in UM.The expressions of CTLA-4 and PD-1 on decidual CD4^＋T cells were reduced as determined by FCM.After cocultrue for 5 days,the TNF-αand IFN-γwere significantly up-regulated in decidual CD4^＋T cells and the secretion of IL-4 was down-regulated.DSCs from UM delivered enhanced co-stimulatory signals and weakened co-inhibitory signals,thus inducing a Th1 immune bias at maternal-fetal interface,which may be one of the causes of UM.

关 键 词：母胎免疫耐受 不明原因自然流产 蜕膜基质细胞 蜕膜CD4^+ T细胞 协同刺激分子 

分 类 号：R392.12[医药卫生—免疫学]