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

作者：Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C. 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 · 发表于：Immunity · 年份：2017 · DOI：10.1016/j.immuni.2017.01.009 · 被引用次数：668 · 研究领域：melanin and skin pigmentation、T-cell and B-cell Immunology、Dermatology and Skin Diseases

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.