小鼠流产模型子宫NK细胞CD25和Foxp3表达特征

Characteristics of CD25 and Foxp3 expression in uterine natural killer cells in a murine model of abortion

探讨CD25和Foxp3分子表达水平与自发性流产小鼠模型流产发病机制的关系。采用磁珠亲和细胞分选术分离小鼠子宫NK细胞,并采用流式细胞术检测NK细胞表达CD25和Foxp3分子的情况,比较自发性流产小鼠CBA/J×DBA/2J和正常对照CBA/J×BALB/c小鼠流产率和上述分子表达水平的差异。在孕早期给CBA/J×DBA/2J雌鼠过继输注CD49^+CD25^+Foxp3^+NK细胞,观察其胚胎丢失率的变化。结果显示,CBA/J×DBA/2J小鼠孕12.5 d胚胎吸收率显著高于CBA/J×BALB/c对照组(分别为23.4%和5.5%,P<0.01),而CBA/J×DBA/2J小鼠孕12.5 d子宫NK细胞CD25和Foxp3阳性率均显著低于CBA/J×BALB/c小鼠(CD25阳性率分别是4.8%和10.5%,Foxp3阳性率分别是0.3%和7.4%,均为P<0.01)。进一步检测发现,这些细胞不表达CD3和CD4分子。此外,输注CD49^+CD25^+Foxp3^+NK细胞可显著降低CBA/J×DBA/2J小鼠孕12.5 d胚胎吸收率(治疗组与对照组分别为8.0%和24.7%,P<0.01)。这些结果提示,CBA/J×DBA/2J小鼠自发性胚胎吸收率增高可能与子宫NK细胞缺乏CD25和Foxp3分子的足量表达有关。

To investigate the relationship between the status of CD25 and Foxp3 expression and murine spontaneous abortion, magnetic affinity cell sorting was used to isolate uterine natural killer （NK） cells, and flow cytometry was performed to deter- mine the status of CD25 and Foxp3 expression in NK cells. The resorption rate of embryos and the proportion of NK cells producing the above-mentioned molecules were compared between CBA/J×DBA/2J and CBA/J×BALB/c mice at day 12.5 of gestation. The adoptive transfer of CD49b＋ CD25＋ Foxp3 ＋ NK ceils was performed at early stage of gestation in CBA/J× DBA/2J mice. It was demonstrated that the resorption rate in CBA/J × DBA/2J mice was significantly higher than that of CBA/J×BALB/c mice （23.4% versus 5.5%, P〈0. 01）, whereas the CD25＋ and Foxp3＋ NK cell percentages in CBA/J × DBA/2J mice were significantly lower than that of CBA/J× BALB/c mice （4.8% and 10.5% for CD25, 0.3% and 7.4% for Foxp3, respectively, P〈0.01 for both）. Further detection showed that no CD3 or CD4 molecules were produced by these cells. The percentage of embryo loss on gestational day 12.5 detected in CBA/J × DBA/2J mice was significantly decreased after the transfer of exogenous CD49b＋CD25＋ Foxp3＋ NK cells （8.0% in the cell-transfer group and 24.7% in control PBS group, respectively） （P〈0.01）. Taken together, these results suggest that the sufficiency of expression of CD25 and Foxp3 molecules by uterine NK ceils in CBA/J × DBA/2J model may be correlated with its increased incidence of embryo resorption.