Central memory T cells are the most effective precursors of resident memory T cells in human skin.

The circulating precursor cells that give rise to human resident memory T cells (T) are poorly characterized. We used an in vitro differentiation system and human skin-grafted mice to study T generation from circulating human memory T cell subsets. In vitro T differentiation was associated with functional changes, including enhanced IL-17A production and FOXP3 expression in CD4 T cells and granzyme B production in CD8 T cells, changes that mirrored the phenotype of T cells in healthy human skin. Effector memory T cells (T) had the highest conversion rate to T in vitro and in vivo, but central memory T cells (T) persisted longer in the circulation, entered the skin in larger numbers, and generated increased numbers of T. In summary, T are highly efficient precursors of human skin T, a feature that may underlie their known association with effective long-term immunity.