Human resident memory T cells hit the road

Skin and other barrier tissues are home to long-lived tissue-resident memory T cells (TRM) that function as sentries capable of rapidly responding to previously encountered antigens. Klicznik et al. investigated the relationship between human skin CD4+ TRM and human blood CD4+ memory T cells expressing skin-homing markers by comparing immunophenotypes, gene expression, and T cell receptor sequences. Shared phenotype, function, and clonotypes between blood and skin CLA+CD103+CD4+ T cells indicated that blood CD4+CLA+CD103+ T cells were previously skin resident. Analysis of immunodeficient mice bearing human skin xenografts revealed that human skin CD4+ TRM can exit the skin, reenter the circulation, and home to secondary human skin sites. These findings establish that there is basal recirculation of human CD4+ skin TRM.