Toxicity of environmentally-relevant concentrations of arsenic on developing T lymphocyte

Arsenic is a ubiquitous environmental contaminant that exists in many inorganic and organic forms. In particular, arsenite is known to induce immunotoxicity in humans and animals. There are still major gaps in our understanding of the mechanism(s) of the immunotoxicity induced by arsenic at environmentally-relevant concentrations. T cells are an essential part of the immune system required for host resistance to infections and protection from cancer. Developing T cells in the thymus have been shown to be particularly prone to arsenite-induced toxicity at low concentrations. Suppression of DNA repair proteins and oxidative stress have been identified as a mechanism of genotoxicity that occurs at low to moderate concentrations. Inhibition of the IL-7 signaling pathway was thought to be responsible for the non-genotoxicity induced by low to moderate doses of arsenic. Interestingly, T cells at different stages of their development had distinct sensitivities to arsenite, which was regulated by arsenite exporters. The current evidence strongly suggests that low to moderate doses of arsenic induces toxic effects in the developing T cells and accumulates to highest levels in the early cells that are least capable to pump out arsenic, which may be the mechanism of the high arsenic sensitivity. Therefore, quantification of the exposure levels should be encouraged in future arsenic toxicity studies.