Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2

Arsenic (As) is a common metalloid which contaminates drinking water in sev eral regions of the world and chronic exposure is associated with skin, lun g, bladder, and kidney cancer. Previous studies suggest that arsenic exposu re leads to a diminution of phytohemaglutinin (PHA) stimulated T cell proli feration in humans. In order to understand the mechanism of this suppressio n, the effect of As was evaluated on the expression of CD25, and IL-2 secre tion in human peripheral blood mononuclear cells (PBMC). Inhibition of prol iferation was observed in all donors studied. Most of the donors did not sh ow any change in the expression of CD25, but IL-2 secretion was inhibited i n 6 of the 7 donors tested. Proliferative inhibition was due to a suboptima l levels of IL-2 secreted by lymphocytes, since the addition of recombinant IL-2 to the cultures reversed in a dose-dependent fashion the inhibitory e ffect of As. The determination of the mRNA of IL-2 and the intracellular IL -2 levels demonstrated that the inhibition is not at the transcriptional le vel. Electron microscopy studies revealed that cellular ultrastructure in G olgi apparatus,mitochondria, cytoskeleton, and perinuclear membrane were al tered. These alterations suggest that due to sodium arsenite effects on cyt oskeleton, the intracellular secretion of proteins is affected, including t he one of IL-2, leading to an impaired proliferation of the T cells when st imulated with PHA.