CD4^+CD25^(high)T细胞和FOXP3在不明原因复发性自然流产中的作用

Role of CD^4+CD25^(high) Regulatory T cells and FOXP3 in Unexplained Recurrent Spontaneous Abortion

【目的】检测不明原因复发性自然流产(URSA)患者外周血及蜕膜的CD4+CD25highT细胞和FOXP3的表达,探讨CD4+CD25highT细胞和FOXP3在母胎免疫耐受中的作用。【方法】选择从2005年9月至2006年6月就诊的154例URSA患者根据就诊时的妊娠状态分成未孕组129例,早期流产组25例;正常早孕要求人工终止妊娠的妇女组50例及正常未孕女性组42例为对照组。收集所有研究对象的外周血及由于计划外妊娠要求行人工流产者和已确认胚胎停育的URSA患者行清宫术后的新鲜蜕膜组织,采用流式细胞仪分析外周血及蜕膜组织CD4+CD25+调节性T细胞及其亚群的比例及FOXP3表达。【结果】①外周血及蜕膜中CD4+CD25highT细胞的比例:正常早孕妇女外周血CD4+CD25highT细胞高于正常未孕妇女及URSA流产组,差异有统计学意义(P<0.01),URSA未孕患者外周血CD4+CD25highT细胞也显著低于正常未孕女性及URSA流产患者(P<0.01);URSA流产患者蜕膜CD4+CD25highT细胞低于正常早孕妇女蜕膜(0.62±0.27vs.1.41±0.31,P<0.01)。②外周血及蜕膜中FOXP3表达比例:正常早孕妇女外周血CD4+CD25highT细胞中FOXP3的表达比例为(95.6±3.6),高于正常未孕妇(92.1±3.4)及URSA流产患者,差异有统计学意义(P<0.01;P<0.05);URSA未孕组患者外周血中FOXP3的表达与正常未孕妇女及URSA流产组之间相比无统计学差异(P>0.05);URSA流产患者蜕膜CD4+CD25highT细胞中FOXP3的表达比例低于正常早孕妇女蜕膜,差异有统计学意义(94.3±3.1vs.97.1±2.2,P<0.01)。【结论】CD4+CD25highT细胞在维持正常妊娠中发挥重要作用,URSA的发生与CD4+CD25highT细胞的减少有关,URSA患者CD4+CD25highT细胞比例下降与FOXP3表达的降低有关。

【Objective】 To detect the proportions of CD4＋ CD25high cells and FOXP3 expression in peripheral blood and decidua of URSA patients and explore the function of CD4 ＋ CD25high cells and FOXP3 expression to maternofetal immunological tolerance. 【Methods】 A total of 154 URSA patients from The Department of Obsterics and Gynecology at The Second Affiliated Hospital of Sun Yat-sen University from September 2005 to June 2006 were recruited to participate in the study. A total of 129 of the URSA patients were in non-pregnant status,and 25 patients were in the condition of early miscarriage confirmed by ultrasonography. Meanwhile,we selected 50 healthy pregnant women who were undergoing elective terminations were all conducted during the first trimester and 42 volunteers who were all normal reproductive women in non-pregnant condition as control groups. Heparinized venous blood was obtained immediately from all study objects and decidual samples were obtained from patients with induced abortion,and URSA patients with spontaneous abortion. The proportions of CD4＋ CD25high cells and FOXP3 expression in peripheral blood and decidua were calculated by flow cytometry. 【Results】 ① In peripheral blood,the proportion of CD4＋ CD25high T cells in normal early pregnant women was significantly higher than that in non-pregnant healthy women and URSA patients with early miscarriage （P 0.01）,and the proportion of CD4＋ CD25high T cells in URSA patients with non-pregnancy were significantly lower than that in URSA patients with early miscarriage and non-pregnant healthy women （P 0.01）. But in decidua,the proportion of CD4＋ CD25high T cells in URSA patients with early miscarriage were lower than that in pregnant healthy women （0.62 ± 0.27 vs. 1.41 ± 0.31,P 0.01）. ② In peripheral blood,the proportion of FOXP3 expression of CD4＋ CD25high cells in early pregnant women was significantly higher than that in normal non-pregnant women and URSA patients （P 0.01; P 0.05）. But the proportion of FOXP3 expression of CD4＋ CD25high cells in URSA patients with non-pregnancy had no statistical significance compared with non-pregnant healthy women and URSA patients with early miscarriage （P 0.05）. In decidua,the proportion of FOXP3 expression in CD4＋ CD25high T cells in URSA patients with early miscarriage were significantly lower than that in pregnant healthy women （94.3 ± 3.1 vs. 97.1 ± 2.2,P 0.01）. 【Conclusion】 CD4＋ CD25high T cells play an important role in maintaining normal pregnancy and its decrease may involve in the pathogenesis of URSA. The decrease of the proportions CD4＋ CD25high T cells in URSA patients is related with the lower FOXP3 expression.