Meggyes Matyas, Nagy David U, Mezosi Livia, Polgar Beata, Szereday Laszlo
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. 2025 Jan 6;26(1):428. doi: 10.3390/ijms26010428.
Pregnancy involves significant immunological changes to support fetal development while protecting the mother from infections. A growing body of evidence supports the importance of immune checkpoint pathways, especially at the maternal-fetal interface, although limited information is available about the peripheral expression of these molecules by CD8+ and CD8- NK cell subsets during the trimesters of pregnancy. Understanding the dynamics of these immune cells and their checkpoint pathways is crucial for elucidating their roles in pregnancy maintenance and potential complications. This study aims to investigate the peripheral expression and functional characteristics of CD8+ and CD8- NK cell subsets throughout pregnancy, providing insights into their contributions to maternal and fetal health. A total of 34 healthy women were enrolled from the first, 30 from the second and 40 from the third trimester of pregnancy. At the same time, 35 healthy age-matched non-pregnant women formed the control group. From peripheral blood, mononuclear cells were separated and stored at -80 °C. CD8+ and CD8- NK cell subsets were analyzed from freshly thawed samples, and surface and intracellular staining was performed using flow cytometric analyses. The proportions of CD56+ NK cells in peripheral blood were similar across groups. While CD8- NKdim cells increased significantly in all trimesters compared to non-pregnant controls, CD8+ NKdim cells showed no significant changes. CD8- NKbright cells had higher frequencies throughout pregnancy, whereas CD8+ NKbright cells significantly increased only in the first and second trimesters. The expression levels of immune checkpoint molecules, such as PD-1 and PD-L1, and cytotoxic-activity-related molecules were stable, with notable perforin and granzyme B increases in CD8- NKbright cells throughout pregnancy. Our study shows that peripheral NK cell populations, especially CD8- subsets, are predominant during pregnancy. This shift suggests a crucial role for CD8- NK cells in balancing maternal immune tolerance and surveillance. The stable expression of immune checkpoint molecules indicates that other regulatory mechanisms may be at work. These findings enhance our understanding of peripheral immune dynamics in pregnancy and suggest that targeting CD8- NKbright cell functions could help manage pregnancy-related immune complications. This research elucidates the stable distribution and functional characteristics of peripheral NK cells during pregnancy, with CD8- subsets being more prevalent. The increased activity of CD8- NKbright cells suggests their critical role in maintaining immune surveillance. Our findings provide a basis for future studies to uncover the mechanisms regulating NK cell function in pregnancy, potentially leading to new treatments for immune-related pregnancy complications.
怀孕涉及显著的免疫变化，以支持胎儿发育，同时保护母亲免受感染。越来越多的证据支持免疫检查点通路的重要性，尤其是在母胎界面，尽管关于这些分子在孕期各阶段由CD8 +和CD8 -自然杀伤（NK）细胞亚群在外周血中的表达信息有限。了解这些免疫细胞及其检查点通路的动态变化对于阐明它们在维持妊娠及潜在并发症中的作用至关重要。本研究旨在调查整个孕期CD8 +和CD8 - NK细胞亚群的外周血表达及功能特征，以深入了解它们对母婴健康的贡献。共招募了34名孕早期健康女性、30名孕中期健康女性和40名孕晚期健康女性。同时，35名年龄匹配的健康非孕女性组成对照组。从外周血中分离出单核细胞并储存在-80°C。对新鲜解冻的样本进行CD8 +和CD8 - NK细胞亚群分析，并使用流式细胞术进行表面和细胞内染色。各组外周血中CD56 + NK细胞的比例相似。与未怀孕对照组相比，所有孕期的CD8 - NKdim细胞均显著增加，而CD8 + NKdim细胞无显著变化。CD8 - NKbright细胞在整个孕期频率较高，而CD8 + NKbright细胞仅在孕早期和孕中期显著增加。免疫检查点分子如PD - 1和PD - L1以及细胞毒性活性相关分子的表达水平稳定，整个孕期CD8 - NKbright细胞中的穿孔素和颗粒酶B显著增加。我们的研究表明，外周NK细胞群体，尤其是CD8 -亚群，在孕期占主导地位。这种转变表明CD8 - NK细胞在平衡母体免疫耐受和监测方面起着关键作用。免疫检查点分子的稳定表达表明可能存在其他调节机制。这些发现加深了我们对孕期外周免疫动态的理解，并表明靶向CD8 - NKbright细胞功能可能有助于管理与妊娠相关的免疫并发症。本研究阐明了孕期外周NK细胞的稳定分布和功能特征，其中CD8 -亚群更为普遍。CD8 - NKbright细胞活性增加表明它们在维持免疫监测中起关键作用。我们的发现为未来研究揭示孕期调节NK细胞功能的机制提供了基础，可能会带来针对免疫相关妊娠并发症的新疗法。
