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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 investigate the effects of CD80 and CD86 on the pregnancy outcomes in spontaneous abortion model and immune tolerance of spleen immune cells to paternal antigens in pregnant rats. Methods Female mice (CBA / J) were mated with BALB / c and DBA / 2 male mice respectively to establish normal pregnancy model CBA / J × BALB / c (20 rats, control group) Abortion model CBA / J × DBA / 2 (20, study group). CBA / J mice were injected intraperitoneally with rat isotype IgG 0 2 mg (10 mice) or rat anti-mouse CD80 and CD86 monoclonal antibodies (10 mice) on day 4 of gestation (implantation). On the 9th day of gestation, the unilateral mixed lymphocyte reaction was used to analyze the proliferative ability of spleen immune cells to the paternal antigens in pregnant rats and to determine the level of interleukin 2 (IL 2) in the cell culture supernatant to study the effect of immunization Tolerance status; on the 14th day of pregnancy, the embryo absorption rate of the two groups was observed. Results (1) In the study group, the embryo absorption rate of pregnant rats injected intraperitoneally with rat IgG was 24.3%, while that of the pregnant mice injected with anti-mouse CD80 and CD86 antibodies was 9.8% The difference was significant (P <0.05). (2) The rat anti-mouse CD80 and CD86 monoclonal antibodies were used to inhibit the proliferation and IL-2 levels of spleen immune cells of pregnant rats on the 9th day of gestation (P <0 05). Conclusion Blocking costimulatory molecules early in pregnancy may induce immune tolerance of spleen immune cells to paternal antigens in pregnant rats so that the pregnancy outcome of spontaneous abortion pregnant rats reaches normal pregnancy level.