Reproductive and Genetic Hospital, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Department of Clinical Laboratory, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Immunol Lett. 2021 Feb;230:42-48. doi: 10.1016/j.imlet.2020.12.005. Epub 2020 Dec 29.
Immune checkpoint molecules are receptors that can transmit inhibitory signals into cells to negatively modulate the immune response. However, their roles in NK cells during normal pregnancy remain poorly understood.
Peripheral blood samples were collected from women during the first, second and third trimesters of pregnancy. Peripheral blood NK (pNK) cells and T cells were analyzed for the expression of the immune checkpoint molecules TIGIT and PD-1 by flow cytometry. In addition, the ability of pNK cells to secret functional molecules was also evaluated.
The expression of TIGIT on pNK cells increased gradually throughout pregnancy, whereas that of PD-1 showed the opposite pattern. However, on T cells, the expression of both TIGIT and PD-1 peaked during early pregnancy, and then declined gradually thereafter. Moreover, the expressions of granzyme B, IFN-γ and CD107a by pNK cells also decreased over the course of pregnancy. Compared with TIGIT- NK cells, TIGIT + NK cells possessed reduced expression of functional molecules.
As pregnancy progressed, the levels of immune checkpoint molecules expressed on pNK cells and T cells changed and the two molecules showed different trends. Furthermore, the secretion of functional molecules from pNK cells was negatively correlated with the trend of TIGIT expression, indicating TIGIT may play an important role in modulating the functions of pNK cells during pregnancy. Further study of TIGIT expression on pNK cells may enhance our understanding of its role in maintaining maternal-fetal tolerance and provide a useful marker for predicting instability during pregnancy.
免疫检查点分子是能够向细胞内传递抑制性信号从而负性调节免疫应答的受体。然而，它们在正常妊娠期间 NK 细胞中的作用仍知之甚少。
收集妊娠 1 、 2 、 3 个时期女性的外周血样本。采用流式细胞术分析外周血 NK （ pNK ）细胞和 T 细胞中免疫检查点分子 TIGIT 和 PD-1 的表达。此外，还评估了 pNK 细胞分泌功能分子的能力。
pNK 细胞上 TIGIT 的表达在整个妊娠期间逐渐增加，而 PD-1 的表达则相反。然而，在 T 细胞上，TIGIT 和 PD-1 的表达均在早孕时达到峰值，随后逐渐下降。此外，pNK 细胞中 granzyme B 、 IFN-γ 和 CD107a 的表达也随着妊娠的进行而降低。与 TIGIT-NK 细胞相比，TIGIT+NK 细胞表达的功能分子减少。
随着妊娠的进展，pNK 细胞和 T 细胞上表达的免疫检查点分子水平发生变化，且两种分子呈现不同的趋势。此外，pNK 细胞功能分子的分泌与 TIGIT 表达的趋势呈负相关，表明 TIGIT 可能在调节妊娠期间 pNK 细胞功能中发挥重要作用。进一步研究 pNK 细胞上 TIGIT 的表达可能有助于我们了解其在维持母胎耐受中的作用，并为预测妊娠不稳定提供有用的标志物。
