T Cells at the Maternal—Fetal Interface: Placental Dynamics in Healthy and Complicated Pregnancy 2260996

Introduction Deciphering the cellular dynamics that sustain tolerance and placental function in health and disease is essential for better therapies. We built a maternal—fetal placental atlas to characterize common immune-mediated pregnancy complications. Methods We collected 69 placenta samples from patients with pregnancy complications including spontaneous preterm birth (n = 10), fetal growth restriction (n = 9), pre-term preeclampsia (n = 10), term preeclampsia (n = 8), type 1 diabetes (n = 10) and healthy controls (n = 21). We profiled samples via multi-modal10x Genomics single cell sequencing: gene expression, CITE-seq and paired T cell receptor, with spatial transcriptomics (Visium HD) in a subset for validation. Results We profiled over 1.2 million placental cells, the largest atlas to date. We identified 114 cell populations, among them 15 T cell subsets. Using genetic demultiplexing we determined fetal or maternal origin of each cell. We found that the majority of the placental T cells are maternal and that the fetal T cells are only naïve or unconventional T cells (γδT cell subsets and MAIT cells). Using paired TCR-seq data we identified T cell clones and associated clonal expansions to specific T cell subsets. Conclusion This comprehensive atlas redefines the placental cellular landscape. Uncovering the different roles that the maternal and fetal T cells have in the cellular micro-environment is key for understanding mechanisms of placental dysregulation. Funding Source NIH/NIAID 1U19AI167899 Topic Categories Immune Mechanisms of Human Disease (HUM)