Persistence of skin-resident memory T cells within an epidermal niche

Significance Tissue-resident memory T cells (TRM) form in the skin where they are retained and can protect against subsequent infection. Using a combination of intravital imaging and mathematical modeling of skin TRM that form after cutaneous herpes simplex virus 1 infection, we reveal that these memory T cells persist at the site of infection for the life of a mouse owing to slow random migration. We also report that TRM compete with dendritic epidermal γδ T cells in skin for local survival signals, suggesting that T cells compete for space within an epidermal niche. Barrier tissues such as the skin contain various populations of immune cells that contribute to protection from infections. These include recently identified tissue-resident memory T cells (TRM). In the skin, these memory CD8+ T cells reside in the epidermis after being recruited to this site by infection or inflammation. In this study, we demonstrate prolonged persistence of epidermal TRM preferentially at the site of prior infection despite sustained migration. Computational simulation of TRM migration within the skin over long periods revealed that the slow rate of random migration effectively constrains these memory cells within the region of skin in which they form. Notably, formation of TRM involved a concomitant local reduction in dendritic epidermal γδ T-cell numbers in the epidermis, indicating that these populations persist in mutual exclusion and may compete for local survival signals. Accordingly, we show that expression of the aryl hydrocarbon receptor, a transcription factor important for dendritic epidermal γδ T-cell maintenance in skin, also contributes to the persistence of skin TRM. Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche.