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

To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8+ T cells 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 T cell 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+ T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species. Altogether, our results show that neonatal CD8+ T cells 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. [Display omitted] •Human neonatal CD8+ T cells have a distinctive transcription and chromatin landscape•Human neonatal CD8+ T cells are less cytotoxic than their adult counterparts•Human neonatal CD8+ T cells are biased toward an innate immune response•This bias could explain the sensitivity of neonates to infections and inflammation Galindo-Albarrán et al. examine the distinct pattern of gene transcription and histone modification landscape in human neonatal CD8+ T cells. Their data suggest that cells are skewed toward an innate immune response and low cytotoxic function. These properties could explain the high susceptibility of neonates to infections and inflammation. Explore the consortium data at the Cell Press IHEC webportal at www.cell.com/consortium/IHEC.