Differential effects of mercury, lead, and cadmium on IL-2 production by Jurkat T cells.

Mercury, lead, and cadmium are widespread and highly toxic pollutants. The aim of this study was to determine the effects of sublethal doses of CH(3)HgCl, CdCl(2), and PbCl(2) on IL-2 production by T lymphocytes. Jurkat T cells were stimulated by triggering CD3 and CD28 molecules before, in conjunction with, or following heavy metal exposure. Heavy metals, individually or mixed together at equimolar concentrations, were used. Results demonstrated that low, noncytotoxic doses of metals induce tyrosine phosphorylation. Mercury and lead (1 microM) inhibit IL-2 production regardless of the state of T cell activation. Cadmium stimulated IL-2 production only in preactivated T cells. Surprisingly, a mixture of these three metals had no effect. We subsequently determined the effects of heavy metals on NFAT (nuclear factors of activated T cells) activity. When cells were stimulated by potent stimulation involving the CD3 and CD28 molecules, an increased NFAT activation was noted when the cells were exposed to mercury and to the metal mixture. Activation with PMA/calcium ionophores indicated that the target of heavy metals is located downstream from PKC and calcium mobilization. These results suggest that the state and mode of T cell activation are important parameters to consider in heavy metal toxicity.