INHIBITION OF HUMAN T-LYMPHOBLAST PROLIFERATION BY HYDROQUINONE

Hydroquinone (HQ) is a major metabolite of benzene and is present in l arge quantities in cigarette tar as a result of the combustion of toba cco leaf pigments. We hypothesize that the immunosuppressive effects o f cigarette smoking are due, in part, to the deposition of large quant ities of HQ in the lungs. Exposure of primary human T lymphoblasts (HT L) in vitro to 50 mu M HQ blocked IL-2-dependent proliferation by >90% with no loss in viability. Inhibition of DNA synthesis was observed i mmediately after the addition of HQ to the cells. However, this effect could be reversed up to 6 hr later by simply washing the cells and re culturing them in the absence of HQ. HQ did not significantly alter in tracellular glutathione levels up to 24 hr later, and the presence of 50 mu M 2-mercaptoethanol or 500 mu M dithiothreitol during the treatm ent did not prevent inhibition of DNA synthesis. HQ did not block bind ing of I-125-IL-2 to the cells, but inhibited the IL-2-dependent progr ession of HTL through S phase of the cell cycle. These observations de monstrate that HQ, in concentrations comparable to those found in ciga rette tar, is a potent inhibitor of IL-2-dependent T cell proliferatio n and may therefore help to explain the potent immunosuppressive effec ts of cigarette smoke on lung T lymphocytes. (C) 1996 Academic Press, Inc.