Heavy-metal mitogenesis: Zn++ and Hg++ induce cellular cytotoxicity and interferon production in murine T lymphocytes.

Splenic and lymph node lymphocytes from Balb/c mice were activated in vitro by the heavy-metal cations, Zn++ and Hg++, as noted by the several-fold increases in 3H-thymidine incorporation at 144 h of culture. Optimal mitogenic concentrations of Zn++ and Hg++ were 200 microM and 10 microM, respectively. Data from experiments using T or B splenic lymphocytes enriched by cell passage over nylon wool columns, through use of athymic Nu/Nu mouse spleen cells, or by cell lysis with monoclonal anti-Thy-1 and antibody plus complement, indicated than Zn++ and Hg++ are mitogens for T cells. Removal of macrophages from spleen cells by treatment with carbonyl iron, followed by cell passage through nylon wool, eliminated the lymphocyte responses to Zn++ and to Hg++. Moreover, addition of macrophage-depleted lymphocytes to monolayers of resident peritoneal macrophages restored the lymphocyte responses to these mitogens. Both Zn++ and Hg++ activated splenic lymphocytes to display lectin-dependent cytotoxicity and to produce acid-labile interferon.