Deoxynivalenol Affects Proliferation and Expression of Activation-Related Molecules in Major Porcine T-Cell Subsets

Toxins (Basel). 2019 Nov 5;11(11):644. doi: 10.3390/toxins11110644.

Abstract

The Fusarium mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide. In vivo, DON modifies the cellular protein synthesis, thereby also affecting the immune system. However, the functional consequences of this are still ill-defined. In this study, peripheral blood mononuclear cells from healthy pigs were incubated with different DON concentrations in the presence of Concanavalin A (ConA), a plant-derived polyclonal T-cell stimulant. T-cell subsets were investigated for proliferation and expression of CD8α, CD27, and CD28, which are involved in activation and costimulation of porcine T cells. A clear decrease in proliferation of all ConA-stimulated major T-cell subsets (CD4+, CD8+, and γδ T cells) was observed in DON concentrations higher than 0.4 µM. This applied in particular to naïve CD4+ and CD8+ T cells. From 0.8 μM onwards, DON induced a reduction of CD8α (CD4+) and CD27 expression (CD4+ and CD8+ T cells). CD28 expression was diminished in CD4+ and CD8+ T cells at a concentration of 1.6 µM DON. None of these effects were observed with the DON-derivative deepoxy-deoxynivalenol (DOM-1) at 16 µM. These results indicate that DON reduces T-cell proliferation and the expression of molecules involved in T-cell activation, providing a molecular basis for some of the described immunosuppressive effects of DON.

Keywords: CD27; CD28; T cells; costimulatory molecules; deoxynivalenol; in vitro; pig; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD28 Antigens / genetics
  • CD8 Antigens / genetics
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Concanavalin A / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / genetics
  • Swine
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology
  • Trichothecenes / toxicity*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics

Substances

  • CD28 Antigens
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Trichothecenes
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Concanavalin A
  • deoxynivalenol