Regulation of Retroviral Infection Unit, Department of Virology, Institut Pasteur, Paris, France.
PLoS One. 2012;7(1):e30017. doi: 10.1371/journal.pone.0030017. Epub 2012 Jan 5.
During the first trimester of human pregnancy, Natural Killer (NK) cells of the maternal uterine mucosa (e.g. decidua) have a unique phenotype and are involved in crucial physiological processes during pregnancy. We investigated whether modifications of the NK receptor repertoire occur during the first trimester of pregnancy. We found significantly decreased expression of KIR2DL1/S1 and KIR2DL2/L3/S2 receptors, NKp30 and NKp44 activatory receptors, and the CD85j (ILT-2) inhibitory receptor. We also observed significantly increased expression of the NKG2D activatory receptor at the decidual NK cell surface. By flow cytometry, we further highlighted an evolution of NK subsets between 8 and 12 weeks of gestation, with a shift from the KIR2DL1/S1⁺/KIR2DL2/L3/S2⁺ subset towards the double negative subset, coupled with a decrease of the CD85j⁺/NKG2D⁻ subset in favour of the CD85j⁻/NKG2D⁺ subset. Furthermore, cell surface expression of NK receptor ligands, including CD85j and NKG2D ligands, has been characterized by flow cytometry on decidual immune CD14⁺ and CD3⁺ cells. HLA-G, the high affinity ligand of CD85j, was detected on both cell types. In contrast, NKG2D ligands ULBP-2 ULBP-3 and MICA/B were not expressed on CD14⁺ and CD3⁺ cells, however a variable expression of ULBP-1 was observed. The ligand expression of KIR2DL1/S1 and KIR2DL2/L3/S2 was also analyzed: the HLA-C molecule was expressed at a low level on some CD14⁺ cells whereas it was not detected on CD3⁺ cell surface. NK receptor ligands are known to be also expressed on the invading placental trophoblast cells. Thus, the phenotypic evolutions of decidual NK cells described in this present study may preserve their activation/inhibition balance during the first trimester of pregnancy.
在人类妊娠的头三个月,母体子宫黏膜(如蜕膜)中的自然杀伤 (NK) 细胞具有独特的表型,并参与妊娠期间的关键生理过程。我们研究了 NK 受体谱是否在妊娠头三个月发生改变。我们发现 KIR2DL1/S1 和 KIR2DL2/L3/S2 受体、NKp30 和 NKp44 激活受体以及 CD85j(ILT-2)抑制性受体的表达显著降低。我们还观察到,在蜕膜 NK 细胞表面,NKG2D 激活受体的表达显著增加。通过流式细胞术,我们进一步强调了妊娠 8 至 12 周之间 NK 亚群的演变,从 KIR2DL1/S1+/KIR2DL2/L3/S2+亚群向双阴性亚群转变,同时 CD85j+/NKG2D−亚群减少,而 CD85j−/NKG2D+亚群增加。此外,通过流式细胞术,我们还对蜕膜免疫 CD14+和 CD3+细胞上 NK 受体配体(包括 CD85j 和 NKG2D 配体)的细胞表面表达进行了特征描述。HLA-G,CD85j 的高亲和力配体,在这两种细胞类型上均有检测到。相比之下,NKG2D 配体 ULBP-2、ULBP-3 和 MICA/B 并未在 CD14+和 CD3+细胞上表达,但观察到 ULBP-1 的表达存在差异。KIR2DL1/S1 和 KIR2DL2/L3/S2 的配体表达也进行了分析:HLA-C 分子在一些 CD14+细胞上低水平表达,而在 CD3+细胞表面则无法检测到。NK 受体配体也已知在入侵的胎盘滋养层细胞上表达。因此,本研究中描述的蜕膜 NK 细胞的表型演变可能在妊娠头三个月维持其激活/抑制平衡。