Zych Michał, Roszczyk Aleksander, Kniotek Monika, Dąbrowski Filip, Zagożdżon Radosław
Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Mazovian Voivodeship, Poland.
1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Starynkiewicza 1, 02-015 Warsaw, Mazovian Voivodeship, Poland.
J Clin Med. 2021 Sep 16;10(18):4182. doi: 10.3390/jcm10184182.
Immune checkpoints are molecules that regulate the function of immune cells and control inflammation processes. An important role in this regard is played by TIM-3/Gal-9 and PD-1/PDL-1 interactions. Previous research performed in a mouse model of pregnancy loss confirmed that blocking TIM-3 could induce fetal loss. Similarly, the PD-1 molecule maintains protective interactions between the mother's immune cells and the fetus. The purpose of this study was to assess the expression of these molecules on a range of T lymphocyte subpopulations from non-pregnant women with recurrent spontaneous abortion (RSA) versus healthy fertile women.
PBMCs were isolated by gradient centrifugation of blood obtained from 12 healthy women and 24 women with RSA and immediately stained for flow cytometry analysis. Standard immunophenotyping of PBMC was performed with the antibodies against classical lymphocyte markers: CD3, CD4, CD8, and CD56. Immune checkpoints were investigated using antibodies against PD-1(CD279) and TIM-3(CD366).
We found that expression of TIM-3 was significantly decreased on CD8+ T lymphocytes in the RSA group, and expression of PD-1 was upregulated on CD4+ T lymphocytes in the RSA group in comparison to the healthy controls.
Considering our findings, therapeutic intervention towards immune checkpoints may be a promising treatment option for recurrent spontaneous abortion.
免疫检查点是调节免疫细胞功能并控制炎症过程的分子。TIM-3/半乳糖凝集素-9和PD-1/程序性死亡受体配体-1的相互作用在这方面发挥着重要作用。先前在流产小鼠模型中进行的研究证实，阻断TIM-3可导致胎儿丢失。同样，PD-1分子维持着母亲免疫细胞与胎儿之间的保护性相互作用。本研究的目的是评估这些分子在复发性自然流产（RSA）的非妊娠女性与健康可育女性的一系列T淋巴细胞亚群上的表达。
通过梯度离心从12名健康女性和24名RSA女性获得的血液中分离外周血单个核细胞（PBMC），并立即进行染色以进行流式细胞术分析。使用针对经典淋巴细胞标志物CD3、CD4、CD8和CD56的抗体对PBMC进行标准免疫表型分析。使用针对PD-1（CD279）和TIM-3（CD366）的抗体研究免疫检查点。
我们发现，与健康对照组相比，RSA组CD8 + T淋巴细胞上TIM-3的表达显著降低，RSA组CD4 + T淋巴细胞上PD-1的表达上调。
考虑到我们的研究结果，针对免疫检查点的治疗干预可能是复发性自然流产的一种有前景的治疗选择。
