| Institution: | 1. Shanghai Key Laboratory of Embryo Original Diseases, The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
These authors contributed equally to the study.;2. Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China;3. Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China;4. Shanghai Key Laboratory of Embryo Original Diseases, The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;5. Department of Automation, Shanghai Jiao Tong University, Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai, PR China;6. Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;7. Reproductive Medicine Center, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai, PR China |
| 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. |
