.Department of Medical Microbiology and Immunology, Medical School, University of Pecs, 12 Szigeti Street, 7624 Pecs, Hungary.
.Janos Szentagothai Research Centre, 20 Ifjusag Street, 7624 Pecs, Hungary.
Int J Mol Sci. 2019 Jan 29;20(3):583. doi: 10.3390/ijms20030583.
The programmed cell death protein 1 (PD-1) receptor has been reported to downregulate T cell activation effectively via binding to its ligands PD-L1 or PD-L2 in a negative co-stimulatory manner. Little is known about the involvement of PD-1 mediated immunoregulation in pregnancy and in pregnancy-related disorders. In this work, we investigated the possible role of the PD-1 co-stimulatory pathway in the pathogenesis of the clinical phase of early-onset preeclampsia characterized by a systemic maternal inflammatory response. We performed a cross-sectional study for comparative analysis of phenotypic and functional characteristics of peripheral blood mononuclear cells in women with early-onset preeclampsia and third-trimester healthy pregnant controls. According to our findings, enhanced expression of either PD-1 or its ligand PD-L1, or both, on the cell surface of effector cells (T cells, natural killer (NK) cells, natural killer T (NKT)-like cells) and Tregs could be observed, but PD-1 expression did not correlate with effector cells exhaustion. These results suggest the failure of the axis to downregulate Th1 responses, contributing thereby to the exaggerated immunoactivation observed in early-onset preeclampsia.
程序性细胞死亡蛋白 1（PD-1）受体已被报道通过与配体 PD-L1 或 PD-L2 以负协同刺激的方式有效地下调 T 细胞的激活。关于 PD-1 介导的免疫调节在妊娠和妊娠相关疾病中的作用知之甚少。在这项工作中，我们研究了 PD-1 共刺激途径在以全身母体炎症反应为特征的早发性子痫前期临床阶段发病机制中的可能作用。我们进行了一项横断面研究，对早发性子痫前期妇女和第三孕期健康孕妇对照的外周血单个核细胞的表型和功能特征进行比较分析。根据我们的发现，可观察到效应细胞（T 细胞、自然杀伤 (NK) 细胞、自然杀伤 T (NKT)-样细胞）和 Treg 细胞表面上的 PD-1 或其配体 PD-L1 或两者的表达增强，但 PD-1 表达与效应细胞耗竭无关。这些结果表明该轴不能下调 Th1 反应，从而导致早发性子痫前期观察到的过度免疫激活。
