title: Prenatal cadmium exposure alters postnatal immune cell development and function.
abstract: Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl(2) (10ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2weeks of age. At 7weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4(+)FoxP3(+)CD25(+) (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8(+)CD223(+) T cells were markedly decreased in the spleens in all offspring at 7weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can result in long term detrimental effects on the immune system of the offspring and these effects are to some extent sex-specific.
authors.affiliation: Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506-9177, USA.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Hanson
authors.forename: Ida
authors.initials: I
authors.lastname: Holásková
authors.forename: Meenal
authors.initials: M
authors.lastname: Elliott
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brundage
authors.forename: Rosana
authors.initials: R
authors.lastname: Schafer
authors.forename: John B
authors.initials: JB
authors.lastname: Barnett
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002104:Cadmium / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012727:Sex Characteristics; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D060168:Thymocytes / Q000187:drug effects* / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D002104:Cadmium; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse