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Immunity. 2017 Feb 21;46(2):287-300. doi: 10.1016/j.immuni.2017.01.009. Epub 2017 Feb 14.

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

Author information

1
Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
2
Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
3
Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden; Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
4
Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
5
Unit for Inflammation, Gastroenterology and Rheumatology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
6
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Building 208, DK-2800 Kongens Lyngby 2800, Denmark.
7
Unit for Endocrinology and Diabetes, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
8
Department of Reconstructive Plastic Surgery, Karolinska University Hospital Solna, Stockholm 171 76, Sweden.
9
Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen 5021, Norway. Electronic address: yenan.bryceson@ki.se.
10
Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden; Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden. Electronic address: liv.eidsmo@ki.se.

Abstract

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.

KEYWORDS:

CD49a; IL-15; Skin; cytotoxicity; granzyme B; immunopathology; perforin; psoriasis; tissue resident T cells; vitiligo

PMID:
28214226
PMCID:
PMC5337619
DOI:
10.1016/j.immuni.2017.01.009
[Indexed for MEDLINE]
Free PMC Article

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