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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Cytotoxicity, Immunologic / immunology*
  • Flow Cytometry
  • Humans
  • Immunologic Memory / immunology
  • Integrin alpha1 / biosynthesis
  • Integrin alpha1 / immunology*
  • Lymphocyte Activation / immunology
  • Microscopy, Confocal
  • Psoriasis / immunology
  • Skin / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Vitiligo / immunology

Substances

  • Integrin alpha1