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

Heavy metal environmental pollutants increase susceptibility of affected in dividuals 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-indu ced 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 mem ory T cell phenotype and utilized the CD4(+) T helper 1 clone, pGL2. We mea sured the effects of the four heavy metals cadmium, lead, mercury, and vana dium on cytokine and proliferation responses by purified CD4(+) T cell to a ntigenic stimulation. Cytokine responses were differentially affected by le ad and vanadium at concentrations that did not affect T cell proliferation in response to antigen. We also determined whether the metal ions induced a poptotic cell death. Mercury induced apoptosis at concentrations as low as 0.5 muM, whereas cadmium required a concentration of 100 muM. Lead (maximal concentration tested was 200 muM) and vanadium (100 muM) did not induce ap optosis. The results suggested that the different heavy metal ions differen tially affected antigen-stimulated responses in T helper cells. These in vi tro systems can now be applied to test whether heavy metal ions alter antig en-induced T cell signal transduction pathways in CD4(+) T helper cells. (C ) 2001 Elsevier Science Ireland Ltd. All rights reserved.