Cutting 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.
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.
Funatake
Castle J
CJ
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis 97331, USA.
Marshall
Nikki B
NB
Steppan
Linda B
LB
Mourich
Dan V
DV
Kerkvliet
Nancy I
NI
D000818:Animals; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006086:Graft vs Host Disease / Q000378:metabolism; D019041:L-Selectin / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D015375:Receptors, Interleukin-2; D019041:L-Selectin