Suppression of allograft immunity by 3,4,5,3',4',5'-hexachlorobiphenyl. I. Effects of exposure on tumor rejection and cytotoxic T cell activity in vivo.
There are conflicting reports in the literature concerning the immunotoxic effects of polychlorinated biphenyls (PCB) on cell-mediated immune responses. In the studies reported here, we show that the in vivo generation of cytotoxic T lymphocytes (CTL) in response to allogeneic tumor challenge is sensitive to suppression by 3,4,5,3',4',5'-hexachlorobiphenyl[(345)2-HxCB], a poorly metabolized, toxic, Ah receptor-binding PCB isomer. C57B1/6 mice treated with a single oral dose of (345)2-HxCB two days prior to the i.p. injection of allogeneic P815 tumor cells exhibited a dose-dependent reduction in peak CTL activity in the spleen. When examined on a kinetic basis, the CTL response was reduced in magnitude on all days examined with no evidence for a shift in the kinetics of the response induced by (345)2-HxCB exposure. (345)2-HxCB exposure prior to antigen challenge (day -14, -7, or -1 relative to P815 injection on day 0) produced significant suppression of the CTL response. (345)2-HxCB exposure 6 weeks prior to antigen challenge was still significantly suppressive, although the reduced degree of suppression suggested that recovery was in progress. When (345)2-HxCB exposure occurred after antigen challenge, significant suppression was produced only when exposure occurred within the first three days of the response, suggesting that, as the CTL matured, their sensitivity to (345)2-HxCB diminished. Clearance of the allogeneic tumor cells from the peritoneal cavity was delayed in (345)2-HxCB-treated mice and was associated with an altered composition of the white blood cell infiltrate in the peritoneal cavity. Symptoms of overt toxicity as well as immunotoxicity were apparent at lower doses of (345)2-HxCB in male as compared to female mice. In addition, interactive effects of (345)2-HxCB exposure and P815 antigen challenge on body weight and thymic involution were observed in both male and female mice. Possible mechanisms for the altered CTL response in (345)2-HxCB-exposed mice are discussed.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006084:Graft Rejection / Q000187:drug effects*; D007166:Immunosuppressive Agents; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011078:Polychlorinated Biphenyls; C027309:3,4,5,3',4',5'-hexachlorobiphenyl