Kerkvliet N I, Baecher-Steppan L
College of Veterinary Medicine, Oregon State University, Corvallis 97331.
Immunopharmacology. 1988 Jul-Aug;16(1):1-12. doi: 10.1016/0162-3109(88)90045-8.
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.
关于多氯联苯（PCB）对细胞介导免疫反应的免疫毒性作用，文献中有相互矛盾的报道。在本文报道的研究中，我们发现，响应同种异体肿瘤攻击时体内细胞毒性T淋巴细胞（CTL）的生成对3,4,5,3',4',5'-六氯联苯[（345）2-HxCB]的抑制敏感，（345）2-HxCB是一种代谢缓慢、有毒、与芳烃受体结合的PCB异构体。在腹腔注射同种异体P815肿瘤细胞前两天经口单次给予（345）2-HxCB的C57B1/6小鼠，脾脏中CTL峰值活性呈剂量依赖性降低。从动力学角度检查时，在所有检查日CTL反应的幅度均降低，没有证据表明（345）2-HxCB暴露诱导的反应动力学发生改变。在抗原攻击前（相对于第0天注射P815为第-14、-7或-1天）暴露于（345）2-HxCB可显著抑制CTL反应。在抗原攻击前6周暴露于（345）2-HxCB仍有显著抑制作用，尽管抑制程度降低表明正在恢复。当在抗原攻击后暴露于（345）2-HxCB时，仅在反应的前三天内暴露才会产生显著抑制，这表明随着CTL成熟，它们对（345）2-HxCB的敏感性降低。在（345）2-HxCB处理的小鼠中，同种异体肿瘤细胞从腹腔的清除延迟，并且与腹腔中白细胞浸润成分的改变有关。与雌性小鼠相比，雄性小鼠在较低剂量的（345）2-HxCB时就出现明显的毒性以及免疫毒性症状。此外，在雄性和雌性小鼠中均观察到（345）2-HxCB暴露与P815抗原攻击对体重和胸腺退化的交互作用。讨论了（345）2-HxCB暴露小鼠中CTL反应改变的可能机制。
