Effects of cadmium and vanadium ions on antigen-induced signaling in CD4(+) T cells

Heavy metal environmental pollutants modulate antigen-directed responses by T lymphocytes, but the molecular mechanisms by which certain metal ions ex ert their effects are only poorly understood. We tested the hypothesis that cadmium and vanadium ions alter antigen-induced T cell signal transduction pathways in CD4(+) T helper cells. We used CD4(+) primary T lymphocytes an d splenic T cells from DO.11.10 T cell receptor transgenic mice. We determi ned the effects of cadmium chloride and sodium orthovanadate at concentrati ons that did not induce apoptotic cell death, but affected cytokine or prol iferation responses to antigenic stimulation. We used electrophoretic mobil ity shift assays to measure effects of cadmium and vanadium ions on antigen -induced activation of the nuclear transcriptional regulator proteins, nucl ear factor-kappaB, cyclic AMP response element binding protein, nuclear fac tor of activated T cells, and activator protein-1. Different signaling path ways lead to activation of these transcription factors. Our results suggest that the two heavy metal ions differentially affect signaling pathways. Th is knowledge will help in the development of molecular epidemiological assa ys. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.