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International Journal of Occupational Medicine and Environmental Health

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Perinatal exposure of mice to TCDD decreases allergic sensitisation through inhibition of IL-4 production rather than T regulatory cell-mediated suppression

Maciej Tarkowski
  • Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Łódź, Poland
/ Barbara Kur
  • Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Łódź, Poland
/ Marek Nocuń
  • Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Łódź, Poland
/ Krystyna Sitarek
  • Laboratory of Toxicity Assessment, Nofer Institute of Occupational Medicine, Łódź, Poland
Published Online: 2010-05-04 | DOI: https://doi.org/10.2478/v.10001-010-0006-7

Perinatal exposure of mice to TCDD decreases allergic sensitisation through inhibition of IL-4 production rather than T regulatory cell-mediated suppression

Objective: The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread, man-made, persistent organic pollutant with high immunotoxic potentials. It suppresses cell-mediated and humoral immune responses through mechanisms dependent on aryl-hydrocarbon receptor expression and immunosuppressive activity of the cells. Most sensitive to TCDD are organisms during fetal and infant life, mostly due to the developmental stage of many biological systems of the host, including immune system. Recent data show that T regulatory cells that have the potential to suppress immune reactions and which develop after TCDD exposure are also responsible for protection from allergy development. Our goal was to investigate if perinatal exposure to TCDD can affect allergic sensitisation and if T reg cells participate in this phenomenon. Materials and Methods: Mice, Balb/c, were perinatally exposed to TCDD or to the carrier. Six weeks old control or exposed mice were sensitised with ovalbumin. Spleen cells of the animals were used to assess the constent of T reg cells by means of flow cytometry. Levels of cytokines were assessed by ELISA technique in supernatants of the cells stimulated with anti-CD3 antibody. As a measure of sensitisation, total IgE and anti-OVA IgE were measured in serum of mice by ELISA method. To assess the function of T reg cells isolated from OVA-sensitised control or TCDD exposed animals we performed transfer studies. Results: Here we show that perinatal exposure to TCDD decreases allergic sensitisation and that this process is related to inhibition of IL-4 synthesis rather than suppression mediated by T regulatory cells. Conclusion: We hypothesise that dioxin exposure can be an important environmental modulator of immunological responses that participate in allergic reactions.

Keywords: Dioxin; T regulatory cells; Allergic sensitization; Animal model; Perinatal exposure

  • Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M, et al. The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci 2006;93(2):223-41.

  • Kerkvliet NI. Recent advances in understanding the mechanisms of TCDD immunotoxicity. Int Immunopharmacol 2002;2 (2-3):277-91. [Crossref] [PubMed]

  • Kerkvliet NI. Immunological effects of chlorinated dibenzo-p-dioxins. Environ Health Perspect 1995;103 Suppl 9:47-53.

  • Colles A, Koppen G, Hanot V, Nelen V, Dewolf MC, Noël E, et al. Fourth WHO-coordinated survey of human milk for persistent organic pollutants (POPs): Belgian results. Chemosphere 2008;73(6):907-14.

  • De Mul A, Bakker MI, Zeilmaker MJ, Traag WA, van Leeuwen S, Hoogenboom R, et al. Dietary exposure to dioxins and dioxin-like PCBs in The Netherlands anno 2004. Regul Toxicol Pharmacol 2008;51(3):278-87. [Web of Science]

  • Wittsiepe J, Furst P, Wilhelm M. The 2005 World Health Organization re-evaluation of TEFs for dioxins and dioxin-like compounds — what are the consequences for German human background levels? Int J Hyg Environ Health 2007;210 (3-4):335-39. [Web of Science]

  • Gehrs BC, Smialowicz RJ. Alterations in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin I. [correction of II]. Effects on the fetus and the neonate. Toxicology 1997;122(3):219-28.

  • Camacho IA, Nagarkatti M, Nagarkatti PS. Evidence for induction of apoptosis in T cells from murine fetal thymus following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Sci 2004;78(1):96-106. [Crossref]

  • Fine JS, Gasiewicz TA, Fiore NC, Silverstone AE. Prothymocyte activity is reduced by perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. J Pharmacol Exp Ther 1990;255(1): 128-32.

  • Holladay SD. Prenatal immunotoxicant exposure and postnatal autoimmune disease. Environ Health Perspect 1999;107 Suppl 5:687-91. [PubMed]

  • Mustafa A, Holladay SD, Goff M, Witonsky SG, Kerr R, Reilly CM, et al. An enhanced postnatal autoimmune profile in 24 week-old C57BL/6 mice developmentally exposed to TCDD. Toxicol Appl Pharmacol 2008;232(1):51-9. [Web of Science]

  • Gehrs BC, Smialowicz RJ. Persistent suppression of delayed-type hypersensitivity in adult F344 rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology 1999;134(1):79-88.

  • Badesha JS, Maliji G, Flaks B. Immunotoxic effects of exposure of rats to xenobiotics via maternal lactation. Part I 2,3,7,8-tetrachlorodibenzo-p-dioxin. Int J Exp Pathol 1995;76(6):425-39.

  • Walker DB, Williams WC, Copeland CB, Smialowicz RJ. Persistent suppression of contact hypersensitivity, and altered T-cell parameters in F344 rats exposed perinatally to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicology 2004;197(1):57-66.

  • Weisglas-Kuperus N, Sas TC, Koopman-Esseboom C, Sas TC, Mulder PG, Sauer PJ, et al. Immunologic effects of background prenatal and postnatal exposure to dioxins and polychlorinated biphenyls in Dutch infants. Pediatr Res 1995;38(3):404-10. [Crossref]

  • Weisglas-Kuperus N, Patandin S, Berbers GA, Sas TC, Mulder PG, Sauer PJ, et al. Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. Environ Health Perspect 2000;108(12): 1203-07. [Crossref]

  • Weisglas-Kuperus N, Vreugdenhil HJ, Mulder PG. Immunological effects of environmental exposure to polychlorinated biphenyls and dioxins in Dutch school children. Toxicol Lett 2004;149(1-3):281-85.

  • Ito T, Inouye K, Fujimaki H, Tohyama C, Nohara K. Mechanism of TCDD-induced suppression of antibody production: effect on T cell-derived cytokine production in the primary immune reaction of mice. Toxicol Sci 2002;70(1):46-54. [Crossref]

  • Nohara K, Fujimaki H, Tsukumo S, Inouye K, Sone H, Tohyama C. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine production in ovalbumin (OVA)-immunized C57Bl/6 mice. Toxicology 2002;172(1):49-58.

  • Inouye K, Pan X, Imai N, Ito T, Takei T, Tohyama C, et al. T cell-derived IL-5 production is a sensitive target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemosphere 2005;60(7): 907-13. [Crossref] [PubMed]

  • Luebke RW, Copeland CB, Daniels M, Lambert AL, Gilmour MI. Suppression of allergic immune responses to house dust mite (HDM) in rats exposed to 2,3,7,8-TCDD. Toxicol Sci 2001;62(1):71-9.

  • Vorderstrasse BA, Steppan LB, Silverstone AE, Kerkvliet NI. Aryl hydrocarbon receptor-deficient mice generate normal immune responses to model antigens and are resistant to TCDD-induced immune suppression. Toxicol Appl Pharmacol 2001;171(3):157-64.

  • Kerkvliet NI, Shepherd DM, Baecher-Steppan L. T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD. Toxicol Appl Pharmacol 2002;185(2):146-52.

  • Funatake CJ, Marshall NB, Steppan LB, Mourich DV, Kerkvliet NI. 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. J Immunol 2005;175(7):4184-8.

  • Marshall NB, Vorachek WR, Steppan LB, Mourich DV, Kerkvliet NI. Functional characterization and gene expression analysis of CD4+ CD25+ regulatory T cells generated in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Immunol 2008;181(4):2382-91.

  • Umetsu DT, DeKruyff RH. The regulation of allergy and asthma. Immunol Rev 2006;212:238-55.

  • Van Wijk F, Wehrens EJ, Nierkens S, Boon L, Kasran A, Pieters R, et al. CD4+CD25+ T cells regulate the intensity of hypersensitivity responses to peanut, but are not decisive in the induction of oral sensitization. Clin Exp Allergy 2007;37(4):572-81. [Web of Science] [Crossref]

  • Von Mutius E. Gene-environment interactions in asthma. J Allergy Clin Immunol 2009;123(1):3-11;quiz 12-13.

  • Von Mutius E, Radon K. Living on a farm: impact on asthma induction and clinical course. Immunol Allergy Clin North Am 2008;28(3):631-47, ix-x. [Web of Science] [Crossref]

  • Wong GW, Chow CM. Childhood asthma epidemiology: insights from comparative studies of rural and urban populations. Pediatr Pulmonol 2008;43(2):107-16. [Web of Science] [Crossref] [PubMed]

  • Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299(6710):1259-60.

  • Schaub B, Liu J, Hoppler S, Schleich I, Huehn J, Olek S, et al. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 2009;123(4):774-82 e5.

  • Geyer H, Scheunert I, Korte F. Bioconcentration potential of organic environmental chemicals in humans. Regul Toxicol Pharmacol 1986;6(4):313-47. [PubMed] [Crossref]

  • Miniero R, De Felip E, Ferri F, di Domenico A. An overview of TCDD half-life in mammals and its correlation to body weight. Chemosphere 2001;43(4-7):839-44. [Crossref]

  • Nakano S, Noguchi T, Takekoshi H, Suzuki G, Nakano M. Maternal-fetal distribution and transfer of dioxins in pregnant women in Japan, and attempts to reduce maternal transfer with Chlorella (Chlorella pyrenoidosa) supplements. Chemosphere 2005;61(9):1244-55.

  • Soechitram SD, Athanasiadou M, Hovander L, Bergman A, Sauer PJ. Fetal exposure to PCBs and their hydroxylated metabolites in a Dutch cohort. Environ Health Perspect 2004;112(11):1208-12.

  • Vercelli D. The regulation of IgE synthesis. Clin Allergy Immunol 2002;16:179-96. [PubMed]

  • Kimata H. 2,3,7,8-tetrachlorodibenzo-p-dioxin selectively enhances spontaneous IgE production in B cells from atopic patients. Int J Hyg Environ Health 2003;206(6):601-4.

  • Fish SC, Donaldson DD, Goldman SJ, Williams CM, Kasaian MT. IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol 2005;174(12): 7716-24.

About the article

Published Online: 2010-05-04

Published in Print: 2010-01-01

Citation Information: International Journal of Occupational Medicine and Environmental Health, ISSN (Online) 1896-494X, ISSN (Print) 1232-1087, DOI: https://doi.org/10.2478/v.10001-010-0006-7. Export Citation

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