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 CdCl2 (10 ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks 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 2 weeks of age. At 7 weeks 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 7 weeks 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.

Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

“…The acquired immune response was determined by assessing anti-streptococcal antibody responses in animals vaccinated with heat-killed Streptococcus pneumoniae . Interestingly, serum antibody responses to both a T-independent (phosphorylcholine, PC) and a T-dependent antigen (Pneumococcal surface protein A, PspA) were dramatically higher in the Cd-treated offspring than the control animals at 7 woa (Hanson et al , 2012). The relative percentage of CD4 + CD25 + FoxP3 + (nTreg) and CD8 + CD223 + T cells in the spleen was also markedly different between the two groups at 7 woa (Hanson et al , 2012).…”

“…Prenatal exposure to an environmentally relevant dose of CdCl 2 (10 ppm w/v) affects thymocyte development of newborn (<12 h old) offspring (Hanson et al , 2010). Follow up studies assessed the effects on the immune system of the offspring at two additional time points following birth (2 and 7 woa) (Hanson et al , 2012). At these ages, thymus and spleen cell populations in Cd-exposed offspring varied very little from controls, with only the macrophage population in males showing a significant increase (Hanson et al , 2012).…”

“…Follow up studies assessed the effects on the immune system of the offspring at two additional time points following birth (2 and 7 woa) (Hanson et al , 2012). At these ages, thymus and spleen cell populations in Cd-exposed offspring varied very little from controls, with only the macrophage population in males showing a significant increase (Hanson et al , 2012). There were, however, changes in spleen cell cytokine production at 7 woa with significantly lower interferon-γ production by male and female offspring.…”

“…There were, however, changes in spleen cell cytokine production at 7 woa with significantly lower interferon-γ production by male and female offspring. Males also had significantly reduced IL-2 production (Hanson et al , 2012). There was no effect on IL-10 and IL-4 production at 7 woa (Hanson et al , 2012).…”

“…Males also had significantly reduced IL-2 production (Hanson et al , 2012). There was no effect on IL-10 and IL-4 production at 7 woa (Hanson et al , 2012). The acquired immune response was determined by assessing anti-streptococcal antibody responses in animals vaccinated with heat-killed Streptococcus pneumoniae .…”