妊娠子宫微环境中uNK细胞NKG2A和NKG2D及其配体表达的研究

目的：研究妊娠子宫微环境中子宫自然杀伤细胞（uNK细胞）NKG2A和NKG2D及其相应配体的表达，探讨NKG2A与NKG2D的不平衡表达在母胎免疫耐受形成中的作用。方法：选择30例孕6-9周的正常妊娠妇女,分离其新鲜蜕膜组织，除去绒毛,分离蜕膜和外周血单个核细胞，采用流式细胞仪测定NK细胞的数量及NKG2A与NKG2D的表达；采用RT-PCR技术检测滋养层组织NKG2A与NKG2D配体人类白细胞抗原-E(HLA-E)、主要组织相容性复合体-Ⅰ类分子相关蛋白A(MICA)mRNA的表达结果：妊娠子宫蜕膜淋巴细胞中NK细胞约占70%,流式细胞分析的结果显示，子宫自然杀伤细胞NKG2A的表达显著高于外周血NK细胞，分别为97.86%±1.75%与33.35%±10.92%（〖AKx-D〗±s），两者差异显著（P<0.05），在滋养层细胞中检测到其配体HLA-E的表达；而与外周血相比，uNK细胞表面NKG2D的表达与之较为相近，分别为93.21%±4.52%与97.80%±1.72%，但两者仍有显著差异（P<0.05）。在滋养层组织未检测到其相应配体MICA mRNA的表达结论：蜕膜中的淋巴细胞主要为NK细胞，其免疫学表型与外周血NK细胞有较大的区别，妊娠期子宫自然杀伤细胞表面高表达抑制性受体NKG2A，同时滋养层组织表达相应的配体人类白细胞抗原-E，这可能是维持母胎界面免疫耐受的重要因素。

Effect of pregnancy uterine microenvironment on the expression of NKG2A,NKG2D and their ligands in decidual NK cells

AIM：To investigate the expression of NKG2A,NKG2D and their ligands in pregnancy uterine micro-environment and to probe the function of NKG2A and NKG2D imbalance expression during the immunotolerance at the fetal-maternal boundary.METHODS：Decidual lymphocytes and peripheral lymphocytes were obtained from 30 women during 6-9 weeks of pregnancy who were undergoing selective termination.FACS technology was used to detect NK cells number and NKG2A,NKG2D expression.RT-PCR was used to investigate HLA-E and MICA mRNA in trophoblast tissue.RESULTS：Natural killer cells predominate,accounting for 70% of pregnancy endometrial lymphocytes.FACS results indicated that NKG2A was significantly increased in decidual NK cells as compared with that in peripheral NK cells,accounting for 97.86%±1.75% and 33.35%±10.92%.The difference between them in NKG2A expression was significant (P<0.05).Although the levels of NKG2D in decidual NK cells were similar to that in peripheral NK cells,accounting for 93.21%±4.52% and 97.80%±1.72%,respectively,the difference between them in NKG2A expression was also significant (P<0.05).At the same time,we found HLA-E mRNA in the trophoblast tissue.There was no proof yet on the expression of NKG2D ligand-MICA on trophoblast.CONCLUSIONS：Natural killer cells are the predominant lymphocytes during the first trimester of decidual tissue.These cells have a great different antigenic phenotype with peripheral natural killer cells.Decidual natural killer cells have high expression of NKG2A and trophoblast tissue expressed HLA-E.This may be an important factor contributing to the immunotolerance at the fetal - maternal boundary during pregnancy.