CD8+ T cells in fetal membranes display a unique phenotype, and their activation is involved in the pathophysiology of spontaneous preterm birth

Abstract 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 cells in 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.