Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function

The in depth understanding of skin resident memory CD8+ T lymphocytes (TRM ) may help uncover strategies for their manipulation during disease. We investigated isolated TRM from healthy human skin, which expressed the residence marker CD69, and compared them to circulating CD8+ T cell populations from the same donors. There were significantly increased proportions of CD8+ CD45RA- CD27- T cells in the skin that expressed low levels KLRG1, CD57, perforin and granzyme B. The CD8+ TRM in skin were therefore phenotypically distinct from circulating CD8+ CD45RA- CD27- T cells that expressed high levels of all these molecules. Nevertheless the activation of CD8+ TRM with TCR/CD28 or IL-2 or IL-15 in vitro induced the expression of granzyme B. Blocking signaling through the inhibitory receptor PD-1 further boosted granzyme B expression. A unique feature of some CD8+ TRM cells was their ability to secrete high levels of TNF-α and IL-2, a cytokine combination that was not frequently seen in circulating CD8+ T cells. The cutaneous CD8+ TRM are therefore diverse and appear to be phenotypically and functionally distinct from circulating cells. Indeed, the surface receptors used to distinguish differentiation stages of blood T cells cannot be applied to T cells in the skin. Furthermore the function of cutaneous TRM appears to be stringently controlled by environmental signals in situ. This article is protected by copyright. All rights reserved.