Triethyllead-induced inhibition of proliferation of normal human lymphocytes through decreased expression of the Tac chain of interleukin 2 receptor.

Triethyllead (Et3Pb+) in concentrations 10(-5) to 10(-6) M has been shown to inhibit several key cellular molecular systems. In order to evaluate the effect of Et3Pb+ on the human immune system, the mitogen-induced cell proliferation of peripheral blood mononuclear cells was studied in the presence of Et3Pb+. Preincubation of normal T-lymphocytes with 10(-6) M Et3Pb+ for 1-4 h, which has been shown to be non-cytotoxic, was sufficient to inhibit subsequent mitogenic-induced cell growth. The Et3Pb(+)-induced impairement of the in vitro proliferation of mitogen-activated normal T-cells was due to a dose-dependent decreased expression of the p55 polypeptide chain (Tac molecule) of the interleukin-2 receptor (IL-2-R), which could not be enhanced by exogeneously added recombinant interleukin 2 (rIL-2). Conversely, the same concentrations of Et3Pb+ could not inhibit the mitogen-induced expression of MHC class II molecules and the transferin receptor on activated T-cells. The impaired membrane expression of p55 on T-cells induced by Et3Pb+ was due to a decrease of Tac mRNA transcripts as showed by Northern blot analysis. This effect seems to be specific since in parallel experiments Et3Pb+ could not inhibit both the accumulation of actin mRNA and the production of IL-2 by Et3Pb(+)-treated mitogen-activated cells. The effect of this organolead compound was also associated with a dose-dependent decrease of the Na(+)-K(+)-ATPase activity of normal lymphocytes. These results indicate that Et3Pb+ could affect specifically T-cell proliferative responses through an imbalance of the IL-2/IL-2-R system.