Skin CD4+ memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation

Abstract

Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4+ T cells in mouse skin are in equilibrium with the circulation at steady state. These cells are dispersed throughout the inter-follicular regions of the dermis and form clusters with antigen presenting cells around hair follicles. After infection or administration of a contact sensitizing agent, there is a sustained increase in skin CD4+ T-cell content, which is confined to the clusters, with a concomitant CCL5-dependent increase in CD4+ T-cell recruitment. Skin CCL5 is derived from CD11b+ cells and CD8+ T cells, with the elimination of the latter decreasing CD4+ T-cell numbers. These results reveal a complex pattern of tissue-retention and equilibration for CD4+ memory T cells in skin, which is altered by infection and inflammation history.