Developmentally determined reduction in CD31 during gestation is associated with CD8Â + T cell effector differentiation in preterm infants

•CD8 + T cell CD31 expression, which dampens T cell receptor signal strength, is reduced in preterm infants at birth.•Cord blood is enriched for effector CD8 + T cells in preterm infants born at younger gestational ages.•Cytokine production at younger gestational ages is enhanced following perinatal inflammatory exposure.•Based on developmentally-determined T cell differences, preterm infants are at risk for immune dysregulation.

Homeostatic T cell proliferation is more robust during human fetal development. In order to understand the relative effect of normal fetal homeostasis and perinatal exposures on CD8 + T cell behavior in PT infants, we characterized umbilical cord blood CD8 + T cells from infants born between 23-42 weeks gestation. Subjects were recruited as part of the NHLBI-sponsored Prematurity and Respiratory Outcomes Program. Cord blood from PT infants had fewer naïve CD8 + T cells and lower regulatory CD31 expression on both naïve and effector, independent of prenatal exposures. CD8 + T cell in vitro effector function was greater at younger gestational ages, an effect that was exaggerated in infants with prior inflammatory exposures. These results suggest that CD8 + T cells earlier in gestation have loss of regulatory co-receptor CD31 and greater effector differentiation, which may place PT neonates at unique risk for CD8 + T cell-mediated inflammation and impaired T cell memory formation.