淋巴细胞免疫治疗对小鼠自然流产模型母胎界面CD80~+表达及妊娠结局的影响

目的:评价CBA/J×DBA/2小鼠配对组合作为反复自然流产模型的生殖力特点,及其与母胎交界CD80表达间的关系,并研究淋巴细胞免疫治疗(lymphocyte immunotherapy,LIT)对CD80表达水平的影响。方法:对CBA/J×DBA/2小鼠的生殖力特点进行为期120d的观察,并与生殖力正常的4种对照组进行比较。另计算15对CBA/J×DBA/2小鼠孕13d的胚胎吸收率,并用CD80-FITC和CD45-PE双色流式细胞术检测CD80细胞在母胎交界面的构成比。为了明确CD80~+细胞的身份,检测了CD3、DX5(NK细胞)和MHC-Ⅱ在CD80细胞群中的表达水平。此外,检测LIT组与未治疗组CBA/J×DBA/2小鼠胚胎吸收率和CD80细胞的阳性率。结果:CBA/J×DBA/2小鼠的流产特点是为孕10d左右的反复流产。CBA/J×DBA/2小鼠孕13d的胚胎吸收率显著高于BALB/c×DBA/2小鼠(30.8％±16.6％vs.7.7％±6.7％,P

Relationship between CD80+ Cell at Fetomaternal Interface and the Fertility Characteristics in Mice Model of Recurrent Spontaneous Abortion

Objectives: To explore the relationship between CD80 expression on lymphocytes at the fetomaternal interface and the fertility characteristics in CBA/J×DBA/2 mice as a model of recurrent spontaneous abortion (RSA) and to investigate the effects of lymphocyte immunotherapy (LIT) on the level of CD80 expression. Methods: The characteristics of fertility in CBA/J× DBA/2 mice were observed in a 120-day period and compared with four normal fertile groups. In another 15 pairs of CBA/J × DBA/2 breedings, resorption rate on day 13 of pregnancy were calculated and the proportion of CD80+ cells at the fetomaternal interface were determined by using two-color flow cytometric analysis, mainly stained with CD80-FITC and CD45-PE. In order to determine the identity of CD80+ cells, the expression levels of CD3(T cell marker) , DX5(NK cell marker) , and MHC-II(antigen presenting cell marker) were detected in this cell population. Furthermore, the resorption rate and the proportion of CD80+ cells among CBA/J×DBA/2 breedings with and without immunotherapy were also determined and compared with normal fertile controls. Results: The characteristics of abortion in CBA/J× DBA/2 mice were recurrent abortion on about day 10 of gestation. The resorption rate in CBA/J× DBA/2 mice was significantly higher than that in BALB/c × DBA/2 mice (30. 8%±16.6% vs. 7. 7%±6. 7%, P<0. 01). Accordingly, the proportion of CD8()+cells evaluated at the fetomaternal interface in CBA/J× DBA/2 mice was also significantly higher (11. 7%± 5. 8% vs. 3. 9%±1. 8% , P<0. 01). Resorption rate of CBA/J×DBA/2 mice underwent LIT was significantly lower than that without LIT, and this decreased rate was correlated with dramatically decreased proportion of CD80+ cells. Conclusion: In CBA/J×DBA/2 mice model, the characteristics of abortion seem to be peri-implantation embryo-resorption. A correlation between early embryonic waste and higher CD80 proportion at the fetomaternal interface suggests that CD80+ cells may be an important determinant in recurrent peri-implantation abortion.