Department of Medical Microbiology and Immunology, Medical School, University of Pécs, 12 Szigeti Street, 7624 Pécs, Hungary.
Janos Szentagothai Research Centre, 20 Ifjusag Street, 7624 Pécs, Hungary.
Int J Mol Sci. 2024 Jul 31;25(15):8378. doi: 10.3390/ijms25158378.
Despite the numerous studies on the clinical aspects of early-onset preeclampsia, our understanding of the immunological consequences of inadequate placenta development remains incomplete. The Th1-predominance characteristic of early-onset preeclampsia significantly impacts maternal immunotolerance, and the role of immune checkpoint molecules in these mechanisms is yet to be fully elucidated. Our study aims to fill these crucial knowledge gaps. A total of 34 pregnant women diagnosed with early-onset preeclampsia and 34 healthy pregnant women were enrolled in this study. A mononuclear cell fragment from the venous blood was separated and frozen. The CD8 and CD8 NK cell subpopulations were identified and compared to their immune checkpoint molecule expressions using multicolor flow cytometry. The serum CD226 levels were measured by ELISA. Based on our measures, the frequency of the CD8 subpopulation was significantly higher than that of the CD8 counterpart in both the NKdim and NKbright subsets. Significantly lower CD226 surface expressions were detected in the preeclamptic group compared to healthy women in all the investigated subpopulations. However, while no difference was observed in the level of the soluble CD226 molecule between the two groups, the CD112 and CD155 surface expressions were significantly different. Our study's findings underscore the significant role of the CD8 and CD8 NK subpopulations in the Th1-dominated immune environment. This deepens our understanding of early-onset preeclampsia and suggests that each subpopulation could contribute to the compensation mechanisms and the restoration of the immunological balance in this condition, a crucial step toward developing effective interventions.
尽管有许多关于早发型子痫前期临床方面的研究,但我们对胎盘发育不全的免疫后果的理解仍不完整。早发型子痫前期以 Th1 优势为特征,这显著影响了母体免疫耐受,而免疫检查点分子在这些机制中的作用尚未完全阐明。我们的研究旨在填补这些关键的知识空白。本研究共纳入 34 例早发型子痫前期孕妇和 34 例健康孕妇。分离并冷冻静脉血的单个核细胞片段。使用多色流式细胞术鉴定和比较 CD8 和 CD8 NK 细胞亚群及其免疫检查点分子的表达。通过 ELISA 测量血清 CD226 水平。根据我们的测量结果,在 NKdim 和 NKbright 亚群中,CD8 亚群的频率均显著高于 CD8 亚群。与健康对照组相比,子痫前期组所有研究亚群的 CD226 表面表达均显著降低。然而,两组之间可溶性 CD226 分子水平无差异,而 CD112 和 CD155 表面表达则存在显著差异。我们的研究结果强调了 CD8 和 CD8 NK 亚群在 Th1 主导的免疫环境中的重要作用。这加深了我们对早发型子痫前期的理解,并表明每个亚群都可能有助于补偿机制和恢复这种情况下的免疫平衡,这是开发有效干预措施的关键步骤。