IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines

J Leukoc Biol. 2009 Aug;86(2):435-43. doi: 10.1189/JLB.0109046.

Abstract

IL-17-producing CD4+ T lymphocytes (Th17) are currently considered relevant participants in the pathogenesis of psoriasis skin lesions. However, little is known about the potential role of IL-17-producing CD8+ T cells, which are also present at the psoriatic plaque. We have addressed the functional characterization of this CD8+ subtype of T lymphocytes from psoriasis patients. Our results show that CD8+IL-17+ cells from psoriasis-inflamed skin tissue produce TNF-alpha and IFN-gamma (Th1-related cytokines) as well as IL-17, IL-21, and IL-22 (Th17-related cytokines) efficiently. A significant up-regulation of the RORC transcription factor is also observed. These cells are refractory to Tregs but show a proliferative response to anti-CD3/CD28 stimulation that is enhanced by IL-12 and IL-15. Blocking of TNF-alpha activity inhibits TCR-mediated activation and IL-17 production. CD8+IL-17+ T cells are cytotoxic cells that display TCR/CD3-mediated cytotoxic abilities to kill target cells. Thus, CD8+IL-17+ T cells share some key features with Th17 cells and exhibit remarkable differential abilities attributable to the CD8+ lineage of T lymphocytes, adding new insights into the functional resources of IL-17-producing cells from human epidermis that could be of potential interest to our understanding of the pathogenesis of psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Lineage / immunology
  • Cytokines / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism*
  • Interleukins / metabolism
  • Lymphocyte Activation / drug effects
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Psoriasis / immunology*
  • Psoriasis / metabolism
  • Psoriasis / physiopathology
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism
  • Skin / immunology*
  • Skin / pathology
  • Skin / physiopathology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies
  • CD28 Antigens
  • CD3 Complex
  • Cytokines
  • Interleukin-17
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma