Abstract
Human exposure to arsenic in drinking water is known to contribute to many different health outcomes such as cancer, diabetes, and cardiopulmonary disease. Several epidemiological studies suggest that T cell function is also altered by drinking water arsenic exposure. However, it is unclear how individual responses differ to various levels of exposure to arsenic. Our laboratory has recently identified differential responses of human peripheral blood mononuclear cell (HPMBC) T cells as measured by polyclonal T cell activation by mitogens during sodium arsenite exposure. T cells from certain healthy individuals exposed to various concentrations (1–100 nM) of arsenite in vitro showed a dose-dependent suppression at these extremely low concentrations (∼0.1–10 ppb) of arsenite, whereas other individuals were not suppressed at low concentrations. In a series of more than 30 normal donors, two individuals were found to be sensitive to low concentration (10 nM equivalent ∼1 ppb drinking water exposure) to sodium arsenite-induced inhibition of T cell proliferation produced by phytohemagglutinin (PHA) and anti-CD3/anti-CD28. In an arsenite-susceptible individual, arsenite suppressed the activation of Th1 (Tbet) cells, and decreased the percentage of cells in the double positive Th17 (RORγt) and Treg (FoxP3) population. While the majority of normal blood donors tested were not susceptible to inhibition of proliferation at the 1–100 nM concentrations of As+3, it was found that all donors were sensitive to suppression by 100 nM monomethylarsonous acid (MMA+3), a key metabolite of arsenite. Thus, our studies demonstrate for the first time that low ppb-equivalent concentrations of As+3 are immunosuppressive to HPBMC T cells in some individuals, but that most donor HPBMC are sensitive to suppression by MMA+3 at environmentally relevant exposure levels.
Highlights
Exposure of human populations to arsenic via drinking water and diet has been determined to be a major worldwide environmental public health issue [1]
Because we are interested in the effects of environmentally relevant concentrations (1–300 ppb drinking water and food equivalent) of As+3 on human T cell function, a series of experiments were conducted in normal Human peripheral blood mononuclear cells (HPBMC) to determine the influence of As+3 on T cell proliferation
In a series of 17 normal human donors, it was found that in vitro exposure to 1– 100 nM As+3 had little effect on T cell proliferation induced by PHA in 15 donors (Figure 1A)
Summary
Exposure of human populations to arsenic via drinking water and diet has been determined to be a major worldwide environmental public health issue [1]. Despite this evidence, there has been inadequate characterization of the effects of arsenic on the immune system of humans. There have been a few studies that have examined the effects of arsenic on human T cell immune function in human populations exposed through drinking water. These studies are important because infections, cancer, and other disease may result from immune suppression. Biswas et al [5] found that humans exposed to arsenic via drinking water in Bangladesh had suppressed T cell responses to concanavallin A, as well as decreased T cell cytokine production
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