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-RM) are poorly characterized. We used an in vitro differentiation system and human skin-grafted mice to study T-RM generation from circulating human memory T cell subsets. In vitro T-RM 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-EM) had the highest conversion rate to T-RM in vitro and in vivo, but central memory T cells (T-CM) persisted longer in the circulation, entered the skin in larger numbers, and generated increased numbers of T-RM. In summary, T-CM are highly efficient precursors of human skin T-RM, a feature that may underlie their known association with effective long-term immunity.