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

• DOI: 10.1016/j.immuni.2017.01.009
• Publication Date: 2017-02-14T19:16:51Z
• Authors: Stanley Cheuk; Heinrich Schlums; Irène Gallais Sér...; Elisa Martini; Samuel C. Chiang; Nicole Marquardt; Anna Gibbs; Ebba Detlofsson; Andrea Introini; Marianne Forkel; Charlotte Höög; Annelie Tjernlund; Jakob Michaëlsson; Lasse Folkersen; Jenny Mjösberg; Lennart Blomqvist; Marcus Ehrström; Mona Ståhle; Yenan T. Bryceson; Liv Eidsmo
• Keywords: Cytotoxicity, Immunologic; 0303 health sciences; Microscopy, Confocal; Immunology; Integrin alpha1; Vitiligo; Cell Separation; CD8-Positive T-Lymphocytes; Flow Cytometry; Lymphocyte Activation; Article; 03 medical and health sciences; CD49a; cytotoxicity; granzyme B; IL-15; immunopathology; perforin; psoriasis; Skin; tissue resident T cells; vitiligo; CD8-Positive T-Lymphocytes; Cell Separation; Cytotoxicity, Immunologic; Flow Cytometry; Humans; Immunologic Memory; Integrin alpha1; Lymphocyte Activation; Microscopy, Confocal; Psoriasis; Skin; T-Lymphocyte Subsets; Vitiligo; Infectious Diseases; T-Lymphocyte Subsets; Immunology and Allergy; Humans; Psoriasis; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being; Immunologic Memory; Skin

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.