Developmental exposure to the potent aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin Impairs the cell-mediated immune response to infection with influenza a virus, but enhances elements of innate immunity.
Based on demonstrated effects on functional immunity in rodent models and supportive evidence from epidemiological studies, it is apparent that developmental exposure to ligands for the aryl hydrocarbon receptor (AhR) has the potential to impair immunity in human populations. Furthermore, due to the high levels of these compounds detected in human breast milk, and the fact that they cross the placenta, it is clear that humans are exposed to AhR ligands during fetal and neonatal development. The current studies were conducted to further characterize the relationship between developmental exposure to TCDD, the most potent AhR agonist, and defects in immune function later in life. Impregnated C57Bl/6 mice were treated with 4 doses of 1 mircog/kg TCDD, given on days 0, 7, and 14 of pregnancy, and 2 days after parturition. Functional immunity was assessed by challenging the adult offspring with influenza virus. Both male and female offspring of the TCDD-treated dams demonstrated impairment of the adaptive immune response, as evidenced by suppressed numbers of T cells and IFNgamma-producing cells in the draining lymph nodes and reduced T cell recruitment to the lung. In contrast, the inflammatory response, including infection-associated pulmonary neutrophilia and IFNgamma levels, was significantly elevated in the developmentally-exposed mice. These functional defects in immunity were not correlated with defects in hematopoeisis, as immune cells in the bone marrow, spleen, and thymus were phenotypically normal in uninfected mice. These results support the idea that immune alterations that arise during development cause persistent and significant changes in immune function.
Vorderstrasse
Beth A
BA
Department of Pharmaceutical Sciences, Pharmacology/Toxicology Program, and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA.
Cundiff
Jennifer A
JA
Lawrence
B Paige
BP