Inhibition of IL-2 responsiveness following exposure to benzo(a)pyrene is due to alterations in accessory cell...

The capacity of lymphocytes from C57Bl/6 X C3H/HeN F1 (B6C3F1) mice to proliferate in vitro following exposure to benzo(a)pyrene (BaP) in vivo or in vitro was examined. Using two assay systems designed to examine the expression of IL-2 receptors without the production of IL-2, a dose-dependent inhibition in IL-2 dependent proliferation was observed in cultures of lymphocytes from animals exposed to BaP in vivo. A similar decrease was seen when lymphocytes were exposed to BaP in vitro. Admixing BaP-exposed and untreated macrophages and T-cells in culture demonstrated that the defect in IL-2 responsiveness resided exclusively within the macrophage compartment. Splenocytes from mice exposed in vivo to BaP showed a marked decrease in the percentage of cells expressing IL-2 receptor following three days of culture. No alterations were seen in the percentage of the Thy 1.2+ and L3T4+ cells. These results suggest that BaP causes an alteration in the macrophage signal(s) needed for the expression of IL-2 responsiveness. The resulting defect in IL-2 dependent proliferation may play a central role in BaP modulation of humoral immunity.