CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

• Published in: Immunity (Cambridge, Mass.) Vol. 46; no. 2; pp. 287 - 300
• Main Authors: Cheuk, Stanley, Schlums, Heinrich, Gallais Sérézal, Irène, Martini, Elisa, Chiang, Samuel C., Marquardt, Nicole, Gibbs, Anna, Detlofsson, Ebba, Introini, Andrea, Forkel, Marianne, Höög, Charlotte, Tjernlund, Annelie, Michaëlsson, Jakob, Folkersen, Lasse, Mjösberg, Jenny, Blomqvist, Lennart, Ehrström, Marcus, Ståhle, Mona, Bryceson, Yenan T., Eidsmo, Liv
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2017; Elsevier Limited; Cell Press
• Subjects: Biopsy; CD49a; CD8-Positive T-Lymphocytes - immunology; Cell Separation; Councils; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Deoxyribonucleic acid; DNA; Experiments; Flow Cytometry; granzyme B; Humans; IL-15; Immunologic Memory - immunology; immunopathology; Integrin alpha1 - biosynthesis; Integrin alpha1 - immunology; Localization; Lymphocyte Activation - immunology; Lymphocytes; Microscopy, Confocal; perforin; Psoriasis; Psoriasis - immunology; Skin; Skin - immunology; T cell receptors; T-Lymphocyte Subsets - immunology; tissue resident T cells; Vitiligo; Vitiligo - immunology; granzyme B; perforin; immunopathology; CD49a; tissue resident T cells; psoriasis; vitiligo; IL-15; Skin; cytotoxicity
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2017.01.009

Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced interferon-γ, whereas CD8+CD49a− Trm cells produced interleukin-17 (IL-17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a– Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases. [Display omitted] •CD49a expression marks CD8+ Trm cells poised for IFN-γ production in human skin•IL-15 drives potent cytotoxic capacity in CD49a+ Trm cells•IL-17 is preferentially produced by CD49a− CD8+ Trm cells in the skin•CD49a+ versus CD49- Trm cell functional dichotomy is preserved in vitiligo and psoriasis Tissue-resident memory T (Trm) cells provide localized adaptive immunity in peripheral tissues. Cheuk et al. identify cytotoxic CD49a+CD8+ Trm cells and IL-17-producing CD49a−CD8+ Trm cells in healthy human skin. The functional dichotomy of pathogenic Trm cells based on CD49a expression is preserved in focal skin diseases vitiligo and psoriasis.