Premature birth and cesarean section affect neonatal CD4+ T cell gene expression and cellular function

In contrast, prematurity induced modest changes in basal gene expression relative to full-term cesarean section neonates. Despite these limited transcriptional differences, CD4⁺ Tcells from preterm neonates displayed enhanced proliferation and increased secretion of inflammatory cytokines IL-13, TNFα, IL-6, and IL-17F, indicating heightened responsiveness. Collectively, our findings suggest that CD4⁺ T cell immune programming begins in utero, as preterm neonates exhibit heightened inflammatory responsiveness.

At term, the mode of delivery further refines this developmental trajectory. Cesarean section is associated with a restrained functional profile, whereas natural birth induces an immune activation signature and enhanced cytokine production. These results provide functional evidence that neonatal CD4⁺ T cell trajectories are established during fetal life and subsequently modulated at birth, underscoring the layered influence of perinatal factors on immune development.