Effects of heavy metal ions on resting and antigen-activated CD4(+) T cells.

Heavy metal environmental pollutants increase susceptibility of affected individuals to bacterial and viral infections, but the mechanisms responsible for this effect are not known. We established cellular in vitro systems to identify molecular targets for the action of heavy metal ions. We used two model systems to determine the effects of heavy metal ions on antigen-induced T lymphocyte responses. The first system was representative of primary antigen responses and utilized CD4(+) primary T lymphocytes derived from DO.11.10 T cell receptor transgenic mice. The second system represented a memory T cell phenotype and utilized the CD4(+) T helper 1 clone, pGL2. We measured the effects of the four heavy metals cadmium, lead, mercury, and vanadium on cytokine and proliferation responses by purified CD4(+) T cell to antigenic stimulation. Cytokine responses were differentially affected by lead and vanadium at concentrations that did not affect T cell proliferation in response to antigen. We also determined whether the metal ions induced apoptotic cell death. Mercury induced apoptosis at concentrations as low as 0.5 microM, whereas cadmium required a concentration of 100 microM. Lead (maximal concentration tested was 200 microM) and vanadium (100 microM) did not induce apoptosis. The results suggested that the different heavy metal ions differentially affected antigen-stimulated responses in T helper cells. These in vitro systems can now be applied to test whether heavy metal ions alter antigen-induced T cell signal transduction pathways in CD4(+) T helper cells.