title: Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4+CD25+Foxp3+ regulatory T cells.
abstract: Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic CD4+CD25+Foxp3+ Treg cells is unknown. Therefore, we investigated the effect of AhR activation on the percentage and number of CD4+CD25+Foxp3+ Treg cells during allergic sensitization in relevant immunological organs. C3H/HeOuJ mice were treated on day 0 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and subsequently sensitized to peanut. On day 8, mice were sacrificed and thymus, spleen and mesenteric lymph nodes (MLN) were isolated. TCDD treatment decreased the number of CD4-CD8-, CD4+CD8+, CD4+CD8- and CD4-CD8+ precursor T cells, but not the number of thymic CD4+CD25+Foxp3+ Treg cells. TCDD treatment increased the number of splenic CD4+CD25+Foxp3+ Treg cells and decreased Th1, Th2 and cytotoxic T cells in the spleen. This appeared to be independent of allergic sensitization. In MLN, TCDD treatment suppressed the increase of the number of CD4+CD25+Foxp3+ Treg cells, Th1, Th2 and cytotoxic T cells induced by peanut sensitization. Together, TCDD treatment preserves thymic CD4+CD25+Foxp3+ Treg cells and decreases peripheral T helper and cytotoxic T cells. This effect of TCDD may contribute to the increased influence of CD4+CD25+Foxp3+ Treg cells on immune mediated responses and to the understanding of how AhR activation modulates immune mediated diseases, including food allergy.
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands.
authors.forename: V J
authors.initials: VJ
authors.lastname: Schulz
authors.forename: J J
authors.initials: JJ
authors.lastname: Smit
authors.forename: M
authors.initials: M
authors.lastname: Bol-Schoenmakers
authors.forename: M B M
authors.initials: MB
authors.lastname: van Duursen
authors.forename: M
authors.initials: M
authors.lastname: van den Berg
authors.forename: R H H
authors.initials: RH
authors.lastname: Pieters
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000276:immunology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon