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Oral tungstate (Na2WO4) exposure reduces adaptive immune responses in mice after challenge

Osterburg, AR;Robinson, CT;Mokashi, V;Stockelman, M;Schwemberger, SJ;Chapman, G;Babcock, GF;

Tungstate (WO) has been identified as a ground water contaminant at military firing ranges and can be absorbed by ingestion. In this study, C57BL6 mice were exposed to sodium tungstate (Na2WO42H2O) (0,2,62.5,125, and 200mg/kg/day) in their drinking water for an initial 28-day screen and in a one-generation (one-gen) model. Twenty-four hours prior to euthanasia, mice were intraperitoneally injected with Staphylococcal enterotoxin B (SEB) (20g/mouse) or saline as controls. After euthanasia, splenocytes and blood were collected and stained with lymphocyte and/or myeloid immunophenotyping panels and analyzed by flow cytometry. In the 28-day and one-gen exposure, statistically significant reductions were observed in the quantities of activated cytotoxic T-cells (TCTL; CD3(+)CD8(+)CD71(+)) and helper T-cells (TH; CD3(+)CD4(+)CD71(+)) from spleens of SEB-treated mice. In the 28-day exposures, CD71(+) TCTL cells were 12.872.05% (SE) in the 0 tungstate (control) group compared to 4.441.42% in the 200mg/kg/day (p<0.001) group. TH cells were 4.851.23% in controls and 2.760.51% in the 200mg/kg/day (p<0.003) group. In the one-gen exposures, TCTL cells were 7.980.49% and 6.330.49% for P and F1 mice after 0mg/kg/day tungstate vs 1.580.23% and 2.520.25% after 200mg/kg/day of tungstate (p<0.001). Similarly, TH cells were reduced to 6.210.39% and 7.200.76%, respectively, for the 0mg/kg/day P and F1 mice, and 2.280.41% and 2.850.53%, respectively, for the 200mg/kg/day tungstate P and F1 groups (p<0.001). In delayed-type hypersensitivity Type IV experiments, tungstate exposure prior to primary and secondary antigen challenge significantly reduced footpad swelling at 20 and 200mg/kg/day. These data indicate that exposure to tungstate can result in immune suppression that may, in turn, reduce host defense against pathogens.