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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 14; pp. 5307 - 5312
• Main Authors: Zaid, Ali, Mackay, Laura K., Rahimpour, Azad, Braun, Asolina, Veldhoen, Marc, Carbone, Francis R., Manton, Jonathan H., Heath, William R., Mueller, Scott N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08-04-2014; National Acad Sciences
• Subjects: Adoptive Transfer; Animals; Biological Sciences; Cell Movement; Dermis; Epidermis; Flow Cytometry; Immunologic Memory; Infections; Intradermal injections; Lesions; Memory; Mice; Mice, Inbred C57BL; Microscopy; Microscopy - methods; Simulation; Skin; Skin - immunology; T cell receptors; T lymphocytes; T-Lymphocytes - immunology; Brownian motion; Langerhans cells; intravital imaging HSV-1 infection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1322292111

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 (T RM). 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 T RM preferentially at the site of prior infection despite sustained migration. Computational simulation of T RM 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 T RM 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 T RM. Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche.