Single-cell gene expression and TCR profiling reveal age-related differences in recent thymic emigrants

Following thymic egress, CD8+ T cells must undergo a post-thymic maturation process to transition from a recent thymic emigrant (RTE) to a mature naïve T cell. Since neonatal animals are comprised of significantly more RTEs, there is a prevailing notion that neonatal CD8+ T cells behave differently than their adult counterparts simply because they have undergone less post-thymic maturation. To test this theory, we leveraged a fate mapping mouse model and single cell sequencing to compare neonatal and adult CD8+ RTEs that have undergone that same amount of post-thymic maturation. Interestingly, we found neonatal and adult CD8+ RTEs exhibit distinct phenotypes, gene expression profiles, TCR usage and functions. These data suggest that neonatal CD8+ T cells are not simply ‘young’ adult CD8+ T cells and that age-related changes in CD8+ T cell functions in early life cannot be solely attributed to differences in the amounts of post-thymic maturation.