Manchorova Diana, Alexandrova Marina, Terzieva Antonia, Vangelov Ivaylo, Djerov Ljubomir, Hristova Iana, Mor Gil, Dimova Tanya
Institute of Biology and Immunology of Reproduction "Acad. Kiril Bratanov", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
University Obstetrics and Gynecology Hospital "Maichin Dom", Medical University, 1431 Sofia, Bulgaria.
Cells. 2025 Apr 29;14(9):649. doi: 10.3390/cells14090649.
Maternal-fetal tolerance mechanisms are crucial during human pregnancy to prevent the immune rejection of the embryo. A well-known mechanism blocking NK-cell cytotoxicity is the interaction of their inhibitory killer-cell immunoglobulin-like receptors (iKIR) with HLA-C molecules on the target cells. In this study, we aimed to investigate the expression of iKIRs (KIR2DL1 and KIR2DL2/3) on the matched decidual and peripheral γδT cells and the localization of HLA-C ligands throughout human pregnancy. The degranulation of γδT cells of pregnant and non-pregnant women in the presence of trophoblast cells was evaluated as well. Our results showed a higher proportion of iKIR-positive γδT cells at the maternal-fetal interface early in human pregnancy compared to the paired blood of pregnant women and full-term pregnancy decidua. In accordance, HLA-C was intensively expressed by the intermediate cytotrophoblasts and decidua-invading extravillous trophoblasts (EVTs) in early but not late pregnancy. Decidual γδT cells during early pregnancy showed higher spontaneous degranulation compared to their blood pairs, but neither decidual nor peripheral γδ T cells increased their degranulation in the presence of Sw71 EVT-like cells. The latter were unable to suppress the higher cytotoxicity of γδT cells, suggesting a complex regulatory landscape beyond NK-like activity inhibition.
母胎耐受机制在人类妊娠期间对于防止胚胎的免疫排斥至关重要。一种众所周知的阻断自然杀伤细胞（NK细胞）细胞毒性的机制是其抑制性杀伤细胞免疫球蛋白样受体（iKIR）与靶细胞上的HLA - C分子相互作用。在本研究中，我们旨在研究iKIR（KIR2DL1和KIR2DL2 / 3）在匹配的蜕膜和外周γδT细胞上的表达以及HLA - C配体在整个人类妊娠期间的定位。我们还评估了滋养层细胞存在时孕妇和非孕妇γδT细胞的脱颗粒情况。我们的结果显示，与孕妇的配对血液和足月妊娠蜕膜相比，在人类妊娠早期母胎界面处iKIR阳性γδT细胞的比例更高。相应地，中间型细胞滋养层细胞和侵入蜕膜的绒毛外滋养层细胞（EVT）在妊娠早期而非晚期强烈表达HLA - C。妊娠早期的蜕膜γδT细胞与其血液配对细胞相比显示出更高的自发脱颗粒，但在Sw71 EVT样细胞存在的情况下，蜕膜和外周γδT细胞均未增加其脱颗粒。后者无法抑制γδT细胞更高的细胞毒性，这表明除了抑制NK样活性之外还存在复杂的调节格局。
