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.


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 content 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.


CONCLUSIONS
We hypothesise that dioxin exposure can be an important environmental modulator of immunological responses that participate in allergic reactions.
Tarkowski
Maciej
M
Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Łódź, Poland. maciekt@imp.lodz.pl
Kur
Barbara
B
Nocuń
Marek
M
Sitarek
Krystyna
K
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D010047:Ovalbumin