TitleCutting edge: activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin generates a population of CD4+ CD25+ cells with characteristics of regulatory T cells.
Publication TypeJournal Article
Year of Publication2005
AuthorsFunatake, CJ, Marshall, NB, Steppan, LB, Mourich, DV, Kerkvliet, NI
JournalJ Immunol
Date Published2005 Oct 1
KeywordsAnimals, Disease Models, Animal, Environmental Pollutants, Gene Expression, Graft vs Host Disease, L-Selectin, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Aryl Hydrocarbon, Receptors, Interleukin-2, Spleen, T-Lymphocytes, Regulatory, Tetrachlorodibenzodioxin

Activation of the aryl hydrocarbon receptor (AhR) by its most potent ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), leads to immune suppression in mice. Although the underlying mechanisms responsible for AhR-mediated immune suppression are not known, previous studies have shown that activation of the AhR must occur within the first 3 days of an immune response and that CD4+ T cells are primary targets. Using the B6-into-B6D2F1 model of an acute graft-vs-host response, we show that activation of AhR in donor T cells leads to the generation of a subpopulation of CD4+ T cells that expresses high levels of CD25, along with CD62L(low), CTLA-4, and glucocorticoid-induced TNFR. These donor-derived CD4+ CD25+ cells also display functional characteristics of regulatory T cells in vitro. These findings suggest a novel role for AhR in the induction of regulatory T cells and provide a new perspective on the mechanisms that underlie the profound immune suppression induced by exposure to TCDD.

Alternate JournalJ. Immunol.
PubMed ID16177056
Grant ListP01ES00040 / ES / NIEHS NIH HHS / United States
P30ES00210 / ES / NIEHS NIH HHS / United States
T32ES07060 / ES / NIEHS NIH HHS / United States