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

Publication date: Available online 14 February 2017
Source:Immunity
Author(s): Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, 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
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.

Graphical abstract

Teaser

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.


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