Co-exposure of arsenic and uranium 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 USEPA maximum contaminant levels (MCL). To address the potential effect of these metals on the activation of naïve CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to arsenic, uranium or a mixture of arsenic and uranium. Arsenic induced a dose dependent effect on activation associated gene expression; targeting immune response genes at the lower dose. Increases in oxidative stress gene expression were observed at the with both arsenic doses. While uranium alone did not significantly alter activation associated gene expression, the mixture of uranium with arsenic demonstrated a combined effect relative to arsenic alone. The results demonstrate the need to investigate metal and metalloid mixtures at environmentally relevant concentrations to better understand the effect of these mixtures on T-cell activation, function and immune dysregulation.