环孢素A诱导自然流产模型孕鼠脾脏CD4^+CD25^+Foxp3^+的调节性T细胞扩增及外周母胎免疫耐受  

Cyclosporine A inducing expansion of the CD4+CD25+Foxp3+ regulatory T cells and peripheral materno-fetal immune tolerance in abortion-prone matings

作　　者：杜美蓉[1] 董琳[1] 周雯慧 闫凤亭 朱晓勇[1] 李大金[1,2] 

机构地区：[1]复旦大学附属妇产科医院研究所生殖免疫研究室 [2]海南医学院附属医院妇产科教研室,海口570102

出　　处：《中国免疫学杂志》2007年第10期920-923,927,共5页Chinese Journal of Immunology

基　　金：国家重点研究项目基金(2006CB0F1009);上海市基础研究重点项目基金(03JC14016);面上项目基金(06ZR14120);复旦大学"985工程"项目(985B36)资助

摘　　要：目的:探讨环孢素A(Cyclosporin A,CsA)对小鼠自然流产模型妊娠预后及外周母胎免疫耐受的影响。方法:以正常妊娠模型CBA/J×BALB/c为对照组,自然流产模型CBA/J×DBA/2为研究组,CBA/J孕鼠于妊娠第4天分别腹腔注射5mg/kgCsA。单向混合淋巴细胞反应分析孕鼠脾脏免疫细胞对父系抗原的增殖能力,ELISA分析上清液IL-2分泌水平,流式细胞术分析脾细胞CD4+CD25+Foxp3+调节性T细胞扩增,并观察两种模型各组胚胎吸收率。结果:于妊娠第4天腹腔注射CsA显著降低自然流产模型孕鼠胚胎吸收率以及孕鼠外周免疫细胞对父系抗原的增殖能力与IL-2分泌(P<0.01,P<0.01,P<0.01),促进脾脏CD4+CD25+Foxp3+调节性T细胞亚群扩增(P<0.01)。结论:孕早期腹腔注射CsA可诱导自然流产模型孕鼠外周免疫细胞对父系抗原的特异性免疫耐受,从而使自然流产模型孕鼠的妊娠结局达到正常妊娠水平,提示CsA可能成为治疗妊娠失败的有效药物。Objective:To explore the effect of CsA on the CD4+CD25+Foxp3+ regulatory T cells and peripheral materno-fetal immune tolerance in abortion-prone matings. Methods:CBA/J female mice were injected intraperitoneally by 5 mg/kg cyclosporin A (CsA) at day 4 of gestation after they were mated to DBA/2 as an abortion-prone model. The CD4+CD25+Foxp3+ regulatory T cells were analyzed by flow cytometry.Immuno-tolerence status and IL-2 level were analyzed by mixed lymphocyte reaction and ELISA at day of 9, 14 of gestation,respectively.Embryo resorption rate was counted at day 14 of gestation.Results:The administration of CsA at the window of implantation resulted in significant expansion of splenic CD4+CD25+Foxp3+ regulatory T cells, decrease of proliferative response and IL-2 production of maternal splenic immuno-competent cells to paternal antigen compared with the control group, thus leading to significantly reduced embryo resorption rate of the abortion-prone model. Conclusion: Administration of CsA at day 4 of gestation,a period of peri-implantation,could induce paternal antigen specific immuno-tolerence,lead the embryo resorption rate of the abortion-prone model to that of normal pregnancy model, which makes CsA a potential medicine for the treatment of pregnancy loss.

关 键 词：环孢素A 自然流产模型 调节性T细胞 免疫耐受 

分 类 号：R392.9[医药卫生—免疫学]