摘要
目的研究髓源抑制性细胞（myeloid-derived suppressor cells，MDSCs）是否在维持正常母胎免疫耐受中发挥关键作用，以及与复发性自然流产（recurrent spontaneous abortion，RSA）的发病有关。方法收集25～35岁非妊娠健康志愿者、正常孕妇、RSA病例各20例外周血，利用流式细胞术分析正常孕妇12、24、36孕周外周血MDSCs的数量变化；比较非妊娠、正常妊娠及RSA妇女外周血MDSCs的数量差异；利用RT-PCR方法检测正常妊娠与RSA病例Arg-1的表达水平；磁珠分选CD8＊T细胞，经3H胸腺嘧啶掺入法检测正常孕妇及RSA病例MDSCs对CD8＊T细胞的抑制作用。结果随着正常孕程进展，MDSCs数量比例增多，且不同孕周间比较差异有统计学意义，孕12周与孕24周比较（P=0．0442），孕24周与孕36周比较（P=0．0233），孕12周与孕36周比较（P=0．0017）。健康非妊娠妇女外周血中MDSCs的比例较低[（0．937±0．127）％]，正常妊娠时其比例最高[（3．777±0．427）％]，RSA病例的MDSCs比例也升高[（2．151±0．185）％]，但显著低于正常孕妇（P=0．0250）；RSA病例外周血MDSCs的Arg-1的表达水平显著降低（P=0．0474），且对CD8＊T细胞增殖的抑制功能显著减弱（P=0．0230）。结论MDSCs在正常妊娠母胎耐受的维持中可能发挥一定作用，RSA患者外周血MDSCs比例显著低于正常孕妇，且抑制T细胞的功能显著降低，可能是RSA发生的机制之一。
Objective To investigate the roles of myeloid derived suppressor cells （MDSCs） in the maintenance of maternal immune tolerance and to analyze their associations with recurrent spontaneous abortion （RSA）. Methods Peripheral blood samples were collected from sixty subjects including non-preg- nant healthy subjects, normal pregnant women and women with recurrent spontaneous abortion aged 25 to 35 years （n = 20）. Flow cytometry analysis was performed to monitor the changes of MDSCs at the 12th, 24th and 36th weeks of gcstational age in three normal pregnant women. The differences with the numbers of MDSCs during the same stage of pregnancy in peripheral blood samples were compared among the three groups by flow cytometry analysis. RT-PCR analysis was used for detection of Arg-1 in women with normal pregnancy and RSA. CDS＋T cells were separated from non-pregnant healthy subjects by using magnetic beads. The immunosuppressive effects of MDSCs, isolated from women with normal pregnancy and RSA, on CD8＋T cells were evaluated by using the 3H thymidine incorporation assay. Results The number of MDSCs increased during normal pregnancy and the differences among different weeks were significant （12th week vs 24th week： P=0. 0442, 24th week vs 36th week： P=0. 0233, 12th week vs 36th week： P=0.0017）. The percentages of MDSCs in peripheral blood of the healthy non-pregnant women were the lowest [ （0. 937± 0. 127）% 1, followed by those in women with RSA [ （2. 151±0. 185 ）% ] and normal pregnant women [ （ 3. 777±0. 427） % ]. There was significant difference with the percentage of MDSCs between women with normal pregnancy and RSA （P = 0. 0250）. Compared with women with normal pregnancy, those with RSA showed significantly decreased levels of Arg-1 （ P = 0. 0474） and suppressed activities of MDSCs against CD8 ＋T cell proliferation （P = 0. 0230）. Conclusion The MDSCs might play an important role in the main- tenance of maternal immune tolerance. Decreased number and inhibited function of MDSCs in the peripheral blood of women with RSA might be responsible for the development of RSA.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2015年第6期448-452,共5页
Chinese Journal of Microbiology and Immunology
基金
杭州市医药卫生科技计划项目(2010B010)；杭州市科技发展计划项目
关键词
髓源抑制性细胞
母胎免疫耐受
复发性自然流产
Myeloid derived suppressor cell
Maternal immune tolerance
Recurrent spontaneous abortion
