Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1 Responses in Behcet's Disease

Immunol Invest. 2017 Jul;46(5):518-525. doi: 10.1080/08820139.2017.1306865. Epub 2017 Apr 17.

Abstract

Objectives: Interleukin-17 (IL-17) has been associated with the pathogenesis of various autoimmune/inflammatory diseases. The aim of this study was to investigate the expression of Th17-related immunity in an innate immunity-dominated vasculitis, namely Behcet's disease (BD).

Methods: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1β, and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon-γ (IFN-γ), and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry.

Results: IL-17 expression by CD8+ and γδ+ T cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17-inducing conditions, production of IFN-γ by CD4+, CD8+, and γδ+ T cells was also higher in BD compared to HC (p < 0.05 in all).

Conclusion: Our results suggest that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. More prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD might be associated with the increased innate responses, early tissue neutrophil infiltrations and late adaptive immunity in BD.

Keywords: Behcet’s disease; Th1 responses; Th17 cells; innate immunity; interleukin-17.

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Behcet Syndrome / immunology*
  • Behcet Syndrome / pathology
  • Case-Control Studies
  • Culture Media / chemistry
  • Culture Media / pharmacology*
  • Female
  • Humans
  • Immunity, Innate
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / metabolism
  • Interleukin-1beta / pharmacology
  • Interleukin-23 / pharmacology
  • Interleukin-6 / pharmacology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / pathology
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • Primary Cell Culture
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / pathology

Substances

  • Culture Media
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Interleukin-6
  • Phytohemagglutinins
  • Interferon-gamma