Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease.

The skin contains a population of tissue-resident memory T cells (T) that is thought to contribute to local tissue homeostasis and protection against environmental injuries. Although information about the regulation, survival program, and pathophysiological roles of T has been obtained from murine studies, little is known about the biology of human cutaneous T Here, we showed that host-derived CD69 αβ memory T cell clones in the epidermis and dermis remain stable and functionally competent for at least 10 years in patients with allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing revealed low expression of genes encoding tissue egress molecules by long-term persisting T in the skin, whereas tissue retention molecules and stem cell markers were displayed by T The transcription factor RUNX3 and the surface molecule galectin-3 were preferentially expressed by host T cells at the RNA and protein levels, suggesting two new markers for human skin T Furthermore, skin lesions from patients developing graft-versus-host disease (GVHD) showed a large number of cytokine-producing host-derived T, suggesting a contribution of these cells to the pathogenesis of GVHD. Together, our studies highlighted the relationship between the local human skin environment and long-term persisting T, which differs from murine skin. Our results also indicated that local tissue inflammation occurs through host-derived T after allogeneic hematopoietic stem cell transplantation.