2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell

Toxicol Lett. 2019 Sep 1;311:49-57. doi: 10.1016/j.toxlet.2019.04.015. Epub 2019 Apr 20.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins, is a persistent and ubiquitous environmental contaminant. Although the immunotoxic effects of TCDD have been reported, the mechanisms underlying these effects are still unclear. In this study, we have determined the toxic effects of TCDD on thymocytes and splenic T cells with in vitro cell culture systems. Magnetically isolated mouse splenic Th cells, Treg cells and the mixed spleen lymphocytes (SLC) were cultured and treated with TCDD and the differentiation of CD4 Th cells was determined by flow cytometery. Our results showed that different concentrations of TCDD caused immunotoxic effects through different toxicological mechanisms in both the purified mouse splenic Th cells and the mixed SLC. The low dose exposure to TCDD triggered regulatory effects in the immune system, while the high dose TCDD exposure resulted in severe immune toxicity. Notably, a decline of Treg subset was observed, suggesting an imbalanced immune regulation by TCDD treatment, as well as a possible decrease of TCDD's indirect effects on bystander immune cells. Our CD4 Th subset co-culture experiments showed that TCDD-induced pathobiology depended on immune cell balance, suggesting that cytokine-induced microenvironments further modulated toxic effects associated with TCDD exposure.

Keywords: AhR; Cell differentiation; Dioxin; Helper T cell; Immune suppression; TCDD.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cellular Microenvironment
  • Coculture Techniques
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / toxicity*
  • Lymphocyte Activation / drug effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Polychlorinated Dibenzodioxins / toxicity*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Spleen / drug effects*
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Thymocytes / drug effects*
  • Thymocytes / immunology
  • Thymocytes / metabolism

Substances

  • Ahr protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Cytokines
  • Environmental Pollutants
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon