Journal article
2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell
Department of Environmental Engineering, Technical University of Denmark1
Environmental Fate & Effect of Chemicals, Department of Environmental Engineering, Technical University of Denmark2
Chinese Academy of Sciences3
Linyi People's Hospital4
University of Copenhagen5
Chinese Academy of Inspection and Quarantine6
Chinese Research Academy of Environmental Sciences7
University Medical Center of Mainz8
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 micro-environments further modulated toxic effects associated with TCDD exposure.
Language: | English |
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Year: | 2019 |
Pages: | 49-57 |
ISSN: | 18793169 and 03784274 |
Types: | Journal article |
DOI: | 10.1016/j.toxlet.2019.04.015 |
ORCIDs: | Pang, Chengfang |
Ahr protein, mouse Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Proliferation Cells, Cultured Cellular Microenvironment Coculture Techniques Cytokines Dose-Response Relationship, Drug Environmental Pollutants Lymphocyte Activation Male Mice, Inbred C57BL Mice, Knockout Phenotype Polychlorinated Dibenzodioxins Receptors, Aryl Hydrocarbon Spleen T-Lymphocytes, Helper-Inducer T-Lymphocytes, Regulatory Thymocytes