CD8+ T cells in fetal membranes display a unique phenotype, and their activation is involved in the pathophysiology of spontaneous preterm birth
CD8+ T cells in fetal membranes display a unique phenotype, and their activation is involved in the pathophysiology of spontaneous preterm birth
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DOI：
10.1002/path.6229
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发表时间：
2023-11-29
影响因子：
7.3
通讯作者：
Zeng，Weihong
中科院分区：
文献类型：
--
作者：
Jiang，Yinan;Lai，Xintong;Zeng，Weihong
早产/分娩是全世界围产期死亡率和发病率的主要原因。先前的研究表明，T细胞对于维持妊娠前三个月的母胎免疫耐受至关重要;然而，它们在分娩和分娩中的表型和功能在很大程度上仍然未知。我们招募了三组分娩时的妇女，对胎盘、胎膜、脐带血和母体外周血进行T细胞免疫表型分析。我们的数据显示，在人类妊娠的第三个三个月期间，T细胞的差异富集，CD 4 +T细胞在脐带血中更容易观察到，而CD 8 +T细胞在胎膜中变得相对更丰富。来自胎膜的CD 4+和CD 8 +T细胞主要由效应记忆T细胞支配，并表现出广泛的活化标志物表达，但归巢受体表达减少。与足月分娩相比，自发性早产患者的胎膜CD 8 +T细胞，尤其是中央记忆亚群的频率显著增加，并显示出更深刻的激活。最后，使用同种异体小鼠模型，我们发现T细胞活化诱导的早产可以通过体内CD 8 +T细胞而不是CD 4 +T细胞的耗竭来缓解。总的来说，我们发现胎膜中的CD 8 +T细胞显示出独特的表型，它们的活化参与了自发性早产的病理生理学，这为早产的免疫机制和预防这种综合征的潜在靶点提供了新的见解。© 2023英国和爱尔兰病理学会。
Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal–fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T‐cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4+T cells being more observable within the umbilical cord blood, whereas CD8+T cells became relatively more abundant in fetal membranes. CD4+and CD8+T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8+T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T‐cell‐activation‐induced preterm birth could be alleviated by the depletion of CD8+T but not CD4+T cellsin vivo. Collectively, we showed that CD8+T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.