2,3,7,8-Tetrachloodibenzo-p-dioxin affects the differentiation of CD4 helper T cell.
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.
['Pang|Chengfang|C|', 'Zhu|Conghui|C|', 'Zhang|Yuanyuan|Y|', 'Ge|Ying|Y|', 'Li|Shujuan|S|', 'Huo|Shouliang|S|', 'Xu|Tuan|T|', 'Stauber|Roland H|RH|', 'Zhao|Bin|B|']
D000818:Animals D051792:Basic Helix-Loop-Helix Transcription Factors D002454:Cell Differentiation D049109:Cell Proliferation D002478:Cells, Cultured D060833:Cellular Microenvironment D018920:Coculture Techniques D016207:Cytokines D004305:Dose-Response Relationship, Drug D004785:Environmental Pollutants D008213:Lymphocyte Activation D008297:Male D008810:Mice, Inbred C57BL D018345:Mice, Knockout D010641:Phenotype D000072317:Polychlorinated Dibenzodioxins D018336:Receptors, Aryl Hydrocarbon D013154:Spleen D006377:T-Lymphocytes, Helper-Inducer D050378:T-Lymphocytes, Regulatory D060168:Thymocytes
Helper T cell TCDD Dioxin AhR Cell differentiation Immune suppression