Reproduction Medical Center, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, 20 Yuhuangding East Road, Yantai, 264000, PR China; Qilu Medical University, 2018 Jiang Meng Road, Zibo, 255300, PR China.
Department of Clinical Laboratory, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, 20 Yuhuangding East Road, Yantai, 264000, PR China.
J Reprod Immunol. 2020 Nov;142:103208. doi: 10.1016/j.jri.2020.103208. Epub 2020 Sep 21.
Immune checkpoint molecules may play a crucial role in safeguarding pregnancy by regulating immune responses at the maternal-fetal interface. In this study, we aim to investigate the expression of PD-1, GITR, HLA-G, and CTLA-4 on T cell subsets in peripheral blood (PB), retroplacental blood (RPB), and cord blood (CB) in normal pregnancy (NP), preeclampsia (PE) and gestational diabetes mellitus (GDM). PB, RPB, and CB were collected immediately after delivery, and the expression of PD-1, GITR, HLA-G, and CTLA-4 on T cell subsets were measured by flow cytometric analysis. The proportions of Tregs in PB, RPB, and CB from NP were significantly higher than those of PE and GDM (P < 0.01, respectively). PD-1 and GITR T cell subsets (CD3, CD4, and CD8 T cells, and Tregs) in PB, as well as PD-1 T cell subsets in RPB from NP, were significantly higher than those of PE and GDM (P < 0.01, respectively). In NP, PE, and GDM, the proportion of PD-1 Tregs was significantly decreased in CB as compared to those of PB and RPB (P < 0.05, respectively) and the proportion of GITR Tregs was significantly higher in PB as compared to those of CB and RPB (P < 0.01, respectively). The proportion of HLA-G Tregs in PB was significantly lower than those of CB and RPB (P < 0.01, respectively). In conclusion, decreased PD-1 and GITR T cell subsets and decreased proportion of Tregs in PB and RPB may play a role in chronic inflammatory immune activation of effector T cells in PE and GDM.
免疫检查点分子可能通过调节母胎界面的免疫反应在保护妊娠中发挥关键作用。本研究旨在探讨 PD-1、GITR、HLA-G 和 CTLA-4 在正常妊娠（NP）、子痫前期（PE）和妊娠期糖尿病（GDM）患者外周血（PB）、蜕膜旁血（RPB）和脐血（CB）中 T 细胞亚群的表达。分娩后立即采集 PB、RPB 和 CB，通过流式细胞术分析测量 PD-1、GITR、HLA-G 和 CTLA-4 在 T 细胞亚群上的表达。NP 组 PB、RPB 和 CB 中的 Tregs 比例明显高于 PE 和 GDM 组（分别为 P < 0.01）。NP 组 PB 中 PD-1 和 GITR T 细胞亚群（CD3、CD4 和 CD8 T 细胞和 Tregs）以及 RPB 中 PD-1 T 细胞亚群均明显高于 PE 和 GDM 组（分别为 P < 0.01）。在 NP、PE 和 GDM 中，与 PB 和 RPB 相比，CB 中 PD-1 Tregs 的比例明显降低（分别为 P < 0.05），而 GITR Tregs 的比例在 PB 中明显高于 CB 和 RPB（分别为 P < 0.01）。PB 中 HLA-G Tregs 的比例明显低于 CB 和 RPB（分别为 P < 0.01）。总之，PB 和 RPB 中 PD-1 和 GITR T 细胞亚群减少和 Tregs 比例降低可能在 PE 和 GDM 中效应 T 细胞的慢性炎症性免疫激活中起作用。
