CD8+ T Cells from Human Neonates Are Biased toward an Innate Immune Response

Abstract

To better understand why human neonates show apoor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8+ Tcells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in Tcell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8+ Tcells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species. Altogether, our results show that neonatal CD8+ Tcells have a specific genetic program biased toward the innate immune response. These findings will contribute to better diagnosis and management of the neonatal immune response.