Reproductive Medicine and Immunology, Obstetrics and Gynecology, Department of Clinical Sciences, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
Reproductive Medicine Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Front Immunol. 2020 Aug 18;11:2025. doi: 10.3389/fimmu.2020.02025. eCollection 2020.
During pregnancy, various immune effectors and molecules participating in the immune-microenvironment establish specific maternal tolerance toward the semi-allogeneic fetus. Activated maternal immune effectors by the trophoblast antigens, such as T helper (Th), T cytotoxic (Tc), T regulatory (Treg), and B cells, are involved in the regulation of adaptive immunity. Recognition of active signal through the T cell receptors stimulate the differentiation of naive CD3CD4 T cells into specific T cell subsets, such as Th1, Th2, Th9, Th17, Th22, and follicular Th cells (Tfh). Each of these subsets has a significant and distinct role in human pregnancy. Th1 immunity, characterized by immune-inflammatory responses, becomes dominant during the peri-implantation period, and the "controlled" Th1 immunity benefits the invading trophoblasts rather than harm. Quickly after the placental implantation, the early inflammatory Th1 immunity is shifted to the Th2 anti-inflammatory immune responses. The predominant Th2 immunity, which overrules the Th1 immunity at the placental implantation site, protects a fetus by balancing Th1 immunity and accommodate fetal and placental development. Moreover, Treg and Th9 cells regulate local inflammatory immune responses, potentially detrimental to the fetus. Th17 cells induce protective immunity against extracellular microbes during pregnancy. However, excessive Th17 immunity may induce uncontrolled neutrophil infiltration at the maternal-fetal interface. Other Th cell subsets such as Tfh cells, also contribute to pregnancy by setting up favorable humoral immunity during pregnancy. However, dysregulation of Th cell immunity during pregnancy may result in obstetrical complications, such as recurrent pregnancy losses (RPL) and preeclampsia (PE). With this review, we intend to deliver a comprehensive overview of CD4 Th cell subsets, including Th1, Th2, Th9, Th17, Th22, and Tfh cells, in human pregnancy by reviewing their roles in normal and pathological pregnancies.
在妊娠期间，各种参与免疫微环境的免疫效应物和分子会对胎儿建立特定的母体耐受。滋养层抗原激活的母体免疫效应物，如辅助性 T 细胞（Th）、细胞毒性 T 细胞（Tc）、调节性 T 细胞（Treg）和 B 细胞，参与适应性免疫的调节。通过 T 细胞受体识别激活信号，刺激初始 CD3CD4 T 细胞分化为特定的 T 细胞亚群，如 Th1、Th2、Th9、Th17、Th22 和滤泡辅助性 T 细胞（Tfh）。这些亚群中的每一个在人类妊娠中都有显著而独特的作用。以免疫炎症反应为特征的 Th1 免疫在着床期占优势，“受控”的 Th1 免疫有利于入侵的滋养层细胞，而不是损害它们。在胎盘植入后不久，早期炎症性 Th1 免疫会向 Th2 抗炎免疫反应转变。优势 Th2 免疫在胎盘植入部位抑制 Th1 免疫，通过平衡 Th1 免疫和适应胎儿及胎盘发育来保护胎儿。此外，Treg 和 Th9 细胞调节局部炎症免疫反应，可能对胎儿有害。Th17 细胞在妊娠期间诱导对外源微生物的保护性免疫。然而，过度的 Th17 免疫可能导致母胎界面不受控制的中性粒细胞浸润。其他 Th 细胞亚群，如 Tfh 细胞，也通过在妊娠期间建立有利的体液免疫来促进妊娠。然而，妊娠期间 Th 细胞免疫的失调可能导致产科并发症，如复发性流产（RPL）和子痫前期（PE）。通过综述，我们旨在通过综述 Th1、Th2、Th9、Th17、Th22 和 Tfh 细胞等 CD4 Th 细胞亚群在正常和病理性妊娠中的作用，全面概述其在人类妊娠中的作用。
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