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

Following thymic egress, CD8+ T cells undergo post-thymic maturation to transition from recent thymic emigrants (RTEs) to mature naive T cells. Although RTEs are phenotypically and functionally distinct from mature naive CD8+ T cells, most studies on RTEs have been performed in adults. As a result, little is known about the behavior of RTEs made in early life, which is when they are most abundant. Here, we used a fate mapping mouse model to compare neonatal and adult CD8+ RTEs and found that they exhibit distinct phenotypes and functions. Paired single-cell transcriptomics and T cell receptor (TCR) sequencing showed that neonatal RTEs exhibit a more effector-like gene expression profile than adult RTEs, and the most pronounced effector-gene bias was found in neonatal RTEs that utilize germline-encoded TCRs. Collectively, these data reveal how the RTE pool changes during development and how TCR usage contributes to phenotypic heterogeneity in the neonatal and adult RTE pools.