干预CD86协同刺激信号在诱导母胎界面Th2型免疫偏倚中的作用

目的 :探讨干预CD86协同刺激信号在诱导母胎界面局部形成Th2型免疫偏倚中的作用。方法 :将正常妊娠模型 (CBA×BALB/c)和自然流产模型 (CBA×DBA/ 2 )CBA孕鼠均分为两组 ,于孕第 4、6、8天 ,对照组腹腔注射大鼠IgG ,实验组腹腔注射大鼠抗小鼠CD86mAb ;孕第 9天 ,ELISA测定母胎界面组织培养上清中Th1型 (IFN γ、TNF α) /Th2型(IL 4、IL 10 )细胞因子表达水平 ,并计算IL 4 /IFN γ、IL 10 /IFN γ比值 ;孕第 12天比较两种模型各组的胚胎吸收率。结果 :正常妊娠模型中 ,干预CD86协同刺激信号对母胎界面原有的Th2型免疫偏离及妊娠预后均无显著影响。自然流产模型中 ,干预CD86协同刺激信号能够诱导母胎界面局部形成Th2型免疫偏倚并显著改善其妊娠预后。结论 :于孕早期 ,干预CD86协同刺激信号能够改善母胎界面局部细胞因子微环境 ,形成维持正常妊娠所需的Th2型免疫偏倚 ,诱导母胎免疫耐受

The role of blockade of CD86 costimulation in Th2 bias inducing at materno-fetal interface

Objective:To study the role of CD86 costimulation in materno fetal immunotolerance induction and the relationship with the Th2 bias at materno fetal interface.Methods:Pregnant DBA/2J mated CBA/J mice with a high embryo resorption rate of 20% to 30% and BALB/c mated CBA/J mice with low embryo resorption rates were studied,with rat anti murine CD86 mAb being administered intraperitoneally at the dosage of 100μg,at days 4,6,8 of gestation.ELISA was applied to analysis the expression of Th type 1/Th type 2 cytokines at materno fetal interface at day 9 of gestation, then the ratios of IL 4/IFN γ and IL 10/IFN γ were counted.Embryo resorption rate was counted at day 12 of gestation.Results:In the model of normal pregnancy,blockade of CD86 costimulation had no significant effects on the original Th2 bias at the materno fetal interface,and the outcomes of gestation had not changed significantly.While in the model of abortion prone,blockade of CD86 costimulation successfully induced a Th2 bias at materno fetal interface.Therefore,the embryo resorbing rates decreased significantly.Conclusion:Anti CD86 mAb is a potent immunosuppressant that prevent from maternal rejection to the allogeneic fetus in a murine model.In vivo blockade of CD86 appears to have apparent effect on inducing Th2 bias at materno fetal interface.