Suppression of allograft immunity by 3,4,5,3',4',5'-hexachlorobiphenyl. I. Effects of exposure on XXXX rejection and cytotoxic T cell activity in vivo.

@entity137 @entity5241 @entity5 @entity19 @entity3215
There are conflicting reports in the literature concerning the immunotoxic effects of @entity3215 ( @entity5241 ) 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 @entity5 challenge is sensitive to suppression by 3,4,5,3',4',5'-hexachlorobiphenyl[(345)2-HxCB], a poorly metabolized, toxic, Ah receptor-binding @entity5241 isomer. C57B1/6 @entity19 treated with a single oral dose of (345)2-HxCB two days prior to the i.p. injection of allogeneic @entity19 @entity5 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 @entity5 cells from the peritoneal cavity was delayed in (345)2-HxCB-treated @entity19 and was associated with an altered composition of the white blood cell infiltrate in the peritoneal cavity. Symptoms of overt @entity137 as well as immunotoxicity were apparent at lower doses of (345)2-HxCB in male as compared to female @entity19 . 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 @entity19 . Possible mechanisms for the altered CTL response in (345)2-HxCB-exposed @entity19 are discussed.
