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

Abstract

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.