CD86协同刺激信号在孕早期母-胎界面Th1/Th2型细胞因子表达调控中的作用

Effect of CD86 costimulation on the modulation of Th1/Th2 cytokines expression at maternal-fetal interface

目的 :探讨CD86协同刺激信号在孕早期母 胎界面Th1 Th2型细胞因子表达调控中的作用。方法 :建立正常妊娠模型CBA×Balb c和自然流产模型CBA×DBA 2。于孕第 4、6、8、10天给CBA孕鼠腹腔注射大鼠IgG作为对照组 ;仅于孕第 4天或于孕第 4、6、8、10天给CBA孕鼠腹腔注射大鼠抗小鼠CD86mAb。孕第 14天计算两种模型各实验组胚胎吸收率R。ELISA法测定孕第 9和第 14天各实验组母 胎界面组织体外培养上清中Th1 Th2型及相关细胞因子 (IL 2、IFN γ、TNF α、IL 4、IL 10、TGF β2 )表达水平。 结果 :孕早期干预CD86协同刺激信号 ,对正常妊娠模型母 胎界面孕第 9和第 14天IL 4、IL 10、TGF β2以及IFN γ、TNF α表达均无显著影响 ,其胚胎吸收率亦无显著变化。自然流产模型中 ,孕早期干预CD86协同刺激信号后 ,孕第 9、第 14天母 胎界面IL 4、IL 10、TGF β2表达均显著增加 (P <0 0 5 ) ;而IFN γ、TNF α表达显著下降 (P <0 0 5 )。胚胎吸收率亦显著下降 (P <0 0 5 )。结论 :孕早期母 胎界面CD86协同刺激信号的调节紊乱可能是触发母体对胚胎产生免疫排斥的重要病理因素 ,于孕早期干预CD86协同刺激信号能够恢复母 胎界面Th1型 Th2型免疫调节的生理平衡 ,从而诱导母 胎免疫耐受。

Objective:To explor the role of CD86 costimulation on the modulation of Th1/Th2 cytokines expression at maternal fetal interface Methods:The abortion prone CBA×DBA/2 matings were established as the models of spontaneous abortion and the nonabortion prone CBA×Balb/c matings were used as the models of normal pregnancy The pregnant CBA females were injected intraperitioneally by rat IgG at day 4,6,8,10 of gestation as control In another two groups, the pregnant CBA females were injected with rat anti mouse CD86mAb at day 4,6,8,10 of gestation or injeted only once at day 4 of gestation The embryo resorbing rate was counted at day 14 of gestation Expression of Th1/Th2 cytokines at the maternal fetal interface at day 9 and day 14 of gestation was determined by ELISA Results:In the model of normal pregnancy, the expression of IL 4, IL 10, TGF β2, IFN γ and TNF α at day 9 and day 14 had not changed significantly after the blockade of CD86 costimulation, neither did the resorbing rates While in the model of abortion prone, the expression of IL 4, IL 10 and TGF β2 increased, but the expression of IFN γ and TNF α declined Therefore, the resorbing rates decreased significantly Conclusion:The disordor in the regulation of CD86 costimulation at the maternal fetal interface may be the important pathogenic factor that may trigger the rejection of fetus Blocking the CD86 costimulation at the early stage of pregnancy could recover the physiological balance of Th1/Th2 at maternal fetal interface and inducing the maternal fetal immune tolerance