The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients

J Invest Dermatol. 1999 Nov;113(5):752-9. doi: 10.1046/j.1523-1747.1999.00749.x.

Abstract

Psoriasis vulgaris is a skin disease potentially mediated by pro-inflammatory cytokines produced by type 1 lesional T cells. The capability of individual T cells to produce these cytokines in lesional skin is not known. In this study we measured the ability of lesional and peripheral blood T cells to produce intracellular interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, and interleukin-10 proteins as detected by flow cytometric analysis. Cytokine synthesis was induced by activation with ionomycin/phorbol myristate acetate (in the presence of Brefeldin A, which inhibits the exocytosis of these cytokines). After stimulation, we found relatively high percentages of epidermal CD8 and CD4 T cells capable of producing interferon-gamma, tumor necrosis factor-alpha, and interleukin-2, whereas few T cells, < 11%, expressed interleukin-4 or interleukin-10. Hence both CD8+ and CD4+ T cells are capable of type 1 effector functions (TC1 and TH1, respectively). This activation scheme was repeated on peripheral blood T cells from psoriatic patients versus healthy controls, where we also found a type 1 bias. In order to evaluate quantitatively the type 1 cytokine bias, we compared the frequency of type 2 interleukin-4 producing versus type 1 interferon-gamma producing T cells in our assay and found a shift towards type 1 producing cells. This shift reveals a type 1 differentiation bias in both lesional areas and in the peripheral blood, which may indicate an imbalance within the T cell population, which is contributing to the chronic or sustained immunologic activation of T cells found in this disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • CD4-CD8 Ratio
  • Cell Differentiation / drug effects
  • Cytokines / biosynthesis*
  • Epidermal Cells*
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / blood
  • Ionomycin / pharmacology
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Psoriasis / blood
  • Psoriasis / pathology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Th1 Cells / cytology
  • Th1 Cells / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate