Co-exposure of uranyl acetate and sodium arsenite differentially alters gene expression in CD3/CD28 activated CD4+ T-cells.

Communities in the western region of the United States experience environmental
exposure to metal mixtures from living in proximity to numerous unremediated abandoned
uranium mines. Metals including arsenic and uranium co-occur in and around these sites at
levels higher than the United States Environmental Protection Agency maximum contaminant
levels. To address the potential effect of these metals on the activation of CD4+ T-cells,
we used RNA sequencing methods to determine the effect of exposure to uranyl acetate, sodium
arsenite or a mixture of uranyl acetate and sodium arsenite. Oxidative stress is a mechanism
proposed for metal toxicity, but findings for uranium differ across cell models. No
significant changes in oxidative stress genes were detected for uranyl acetate, in contrast
to sodium arsenite. Sodium arsenite induced a dose dependent effect on activation associated
gene expression, targeting immune response genes at the lower dose. While uranyl acetate
alone did not significantly alter activation associated gene expression, the mixture
demonstrated a combined effect relative to sodium arsenite alone. The results demonstrate
the need to investigate uranium alone and in metalloid mixtures at environmentally relevant
concentrations to better understand the toxicological impact of these mixtures on T-cell
activation, function and immune dysregulation.