妊娠早期阻断协同刺激分子诱导自然流产模型孕鼠脾脏细胞母-胎免疫耐受的研究  

Inducing peripheral materno-fetal immuno-tolerance by blockade of costimulatory signal at early stage of gestation of the abortion-prone murine model

作　　者：金莉萍[1] 李大金[1] 王明雁[1] 朱晓勇[1] 朱影[1] 孟毅[1] 袁敏敏[1] 

机构地区：[1]复旦大学附属妇产科医院生殖免疫研究所,上海200011

出　　处：《中华妇产科杂志》2004年第4期234-237,共4页Chinese Journal of Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目 (3 9770 773);计划生育药具国家重点实验室课题基金资助项目(B2 0 2 1)

摘　　要：目的　探讨阻断协同刺激分子———CD80 和CD86对自然流产模型孕鼠妊娠结局及孕鼠脾脏免疫细胞对父系抗原免疫耐受状态的影响。方法　将雌性小鼠 (CBA/J)分别与BALB/c及DBA/2两种雄性小鼠合笼交配 ,分别建立正常妊娠模型CBA/J×BALB/c( 2 0只 ,对照组 )和自然流产模型CBA/J×DBA/2 ( 2 0只 ,研究组 )。CBA/J小鼠于妊娠第 4天 (着床期 )腹腔分别注射大鼠同型IgG 0 2mg( 10只 ) ,或大鼠抗小鼠CD80 和CD86单克隆抗体 ( 10只 )。妊娠第 9天 ,采用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 ,并测定细胞培养上清液中白细胞介素 2(IL 2 )水平 ,以研究脾脏细胞母 胎免疫耐受状态 ;妊娠第 14天观察两组的胚胎吸收率。结果　 ( 1)研究组中 ,腹腔注射大鼠IgG的孕鼠胚胎吸收率为 2 4 3% ,而注射大鼠抗小鼠CD80 和CD86单克隆抗体的孕鼠胚胎吸收率为 9 8% ,两者比较 ,差异有显著性 (P <0 0 5 )。 ( 2 )应用大鼠抗小鼠CD80 和CD86单克隆抗体 ,使妊娠 9d的孕鼠脾脏免疫细胞对父系抗原的增殖能力及IL 2水平显著下降(P <0 0 5 )。结论　孕早期阻断协同刺激分子 ,可诱导产生孕鼠脾脏免疫细胞对父系抗原的免疫耐受 ,从而使自然流产模型孕鼠的妊娠结局达到正常妊娠水平。Objective To study effect of blockade of costimulatory signal CD 80 ,CD 86 at the early stage of gestation on the maternal peripheral immuno tolerance status to paternal antigen and pregnant outcome of murine abortion prone model Methods The experiments were performed in two groups, using CBA/J×BALB/c matings as the normal pregnancy model and CBA/J×DBA/2 matings as the abortion prone model The pregnant CBA/J mice which had mated with DBA/2 or BALB/c male mice respectively were injected intraperitoneally with purified rat isotype IgG or purified rat anti mouse CD 80 , CD 86 mAb at day 4 of gestation (time of implantation) The proliferation response of maternal splenic immuno competent cells to paternal splenic cells as stimulator was analyzed by one way mixed lymphocyte reaction, and IL 2 production was assayed by ELISA to evaluate the immuno tolerance of maternal peripheral immuno competent cells to paternal antigen at day 9 of gestation The embryo resorption rate was counted at day 14 of gestation Results In the CBA/J×DBA/2 matings, anti CD 80 ,CD 86 mAb administered at day 4 of gestation reduced significantly the embryo resorption rate, and induced a significantly lower proliferation response and IL 2 production by maternal splenic immuno competent cells to paternal antigen compared with rat isotype IgG Conclusions In vivo blockade of costimulatory signal at day 4 of gestation can induce the immuno tolerance of maternal peripheral immuno competent cells to paternal antigen, thus leading the embryo resorption rate of the abortion prone model to that of normal pregnancy model

关 键 词：自然流产 脾脏细胞 母-胎免疫耐受 CD80抗原 CD抗原 膜糖蛋白类 妊娠结局 

分 类 号：R714.21[医药卫生—妇产科学]