Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans [scRNA-seq]

The development of human adaptive immunity progresses faster than previously appreciated, with the emergence of memory CD4+ T cells alongside regulatory T (Treg) cells by the second trimester of pregnancy. We previously identified a prenatal-specific subset of PLZF+ CD4+ T cells with heightened effector potential that accounted for most memory T cells in the developing intestine and accumulated in the cord blood of infants exposed to prenatal inflammatory pathologies. However, the signals that drive their tissue distribution and effector maturation are unknown. Here, we define the transcriptional and functional heterogeneity of prenatal PLZF+ CD4+ T cells and identify compartmentalization of Th-like effector function across the small intestine (SI) and mesenteric lymph nodes (MLN). Prenatal intestine PLZF+CD4+ T cells were isolated by Fluorescence-activated cell sorting (FACS) using proxy markers, and analyzed using scRNAseq.