妊娠浓度的雌激素增强调节性T细胞抑制功能的实验研究  

Enhanced Suppression of CD_4^+CD_(25)^+ Regulatory T Cells by Pregnant Level of Estrogen in Vitro

作　　者：汪理[1] 林星光[1] 陈忠华 昌盛[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所、国家教育部／卫生部重点实验室,武汉430030

出　　处：《医药导报》2009年第4期411-414,共4页Herald of Medicine

基　　金：国家自然科学基金面上项目资助(基金编号:30500468);“973”计划专项基金(基金编号:2009CB522400)

摘　　要：目的体外观察妊娠浓度的雌激素(E2)能否诱导天然CD4+CD25+Treg细胞的增殖并增强其抑制功能。方法天然CD4+CD25+Treg细胞的增殖检测:CFSE标记天然CD4+CD25+Treg细胞作为反应细胞预先经妊娠水平的E2孵育2h后,加入抗CD3/CD28单抗体外培养。以是否经E2孵育或加入抗CD3/CD28单抗分为2个阴性对照组和空白对照组。120h后检测天然CD4+CD25+Treg细胞的增殖情况。天然CD4+CD25+Treg细胞的功能检测:以CFSE标记CD4+CD25naiveT细胞作为反应细胞与预先经E2孵育2h的天然CD4+CD25+Treg细胞共培养,并于其中加入抗CD3/CD28单抗。以是否经E2孵育或加入抗CD3/CD28单抗分为2个阴性对照组和空白对照组。120h后检测CD4+CD2-5naiveT细胞的增殖情况。结果增殖检测提示两阴性对照组与空白对照组天然CD4+CD25+Treg细胞无明显增殖,而实验组则较对照组增殖明显;功能检测提示空白对照组标记细胞不发生明显增殖,阴性对照组A中标记细胞增殖明显;实验组标记细胞增殖能力在经E2孵育的天然CD4+CD25+Treg细胞作用下受到明显抑制,与阴性对照组A和空白对照组差异均有显著性;阴性对照组中标记细胞的增殖也被明显抑制,与阴性对照组A比较差异有显著性,但同时其增殖抑制作用又弱于实验组,差异也有显著性。结论体外实验表明,妊娠状态下高水平的雌激素能通过促使天然CD+CD+Treg细胞的扩增而增强其抑制功能。Objective To investigate whether the pregnant-level estrogen induce the expansion of CD4＋ CD25＋ regulatory T cells and its suppression activity in vitro. Methods ① CD4＋ CD25＋ regulatory T cells labelled with CFSE were stimulated with anti-CD3 and anti-CD28 mAbs or PBS in the presence and absence of pregnant level estrogen （ E2 ） （ experimental group, control group A and control group B）, or no any stimulus instead of PBS （placebo group）. ②CFSE-labelled CD4＋ CD25＋ naive T cells were cultured with CD4＋ CD25＋ regulatory T cells, which were pretreated for 2 hours with estrogen or not, and stimulated with anti- CD3 and anti-CD2s mAbs or PBS （experimental group, control group A and control group B）. As placebo group, CFSE-labelled CD4＋ CD25＋ naive T ceils were treated only with PBS. After 120 hours, the proliferation of labelled cells was detected by FACS and analyzed by Modfit LT soft. Results Stimulated by anti-CD3 and anti-CD2s mAbs in 120 h, the proliferation index （PI） of CD4＋ CD25＋ regulatory T cells in experimental group were significantly higher than that in two control groups and placebo group. The proliferation of CFSE-labelled CD4＋＋ CD25＋ naive T cells mediated with anti-CD3 and anti-CD2s mAbs was inhibited by CD4＋ CD25＋ regulatory T cells, estrogen pretreated CD4＋ CD25＋ regulatory T cells could further enhance this effect. Conclusion It suggested that high level of estrogen in gestation can induce the expansion of CD4＋ CD25＋ regulatory T cells and enhance its suppression, and may play a pivotal role in the matemal-feto tolerance.

关 键 词：雌激素 妊娠 天然CD4+CD2+5调节性T细胞 增殖 

分 类 号：R977.1[医药卫生—药品] R392.1[医药卫生—药学]