Lang D S, Becker S, Devlin R B, Koren H S
Center of Environmental Medicine and Lung Biology, University of North Carolina, USA.
Toxicol Lett. 1996 Nov;88(1-3):317-25. doi: 10.1016/0378-4274(96)03756-3.
In contrast to the well documented immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans accidentally or occupationally exposed to dioxin. More recently, a dose-dependent decrease of specific subpopulations of mitogen-activated human peripheral blood lymphocytes (PBL), including helper-inducer/memory cells (CD4+CD29+) and B cells (CD20+), was reported after in vitro treatment with dioxin concentrations as low as 10(-12)-10(-14) M TCDD [1]. Therefore, the direct effects of dioxin on human PBL subpopulations have been studied in more detail, in order to assess the availability of a sensitive indicator system for human dioxin exposure. PBL from healthy volunteers were stimulated with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody (OKT3) and treated with 10(-7)-10(-14) M TCDD for 3-4 days. Cytochrome P450 (CYP1A1) enzyme induction was determined by the ethoxy-resorufin-O-deethylase (EROD) assay. Percentages of the different lymphocytes subsets, including CD2 (T cells), CD4, CD45 RA (suppressor-inducer/ virgin T cells), CD4, CD29, CD8, CD19 (B cells), as well as interleukin 2 (IL-2) receptor (CD25) and class II antigen (human leukocyte antigen HLA-DR) expression, were analyzed by flow cytometry. The proliferative activity was determined by 3H-thymidine uptake after 3-4 days of culture. In the present study, all stimulated lymphocyte cultures showed a significant increase of CYP1A1 activity at dioxin concentrations of 10(-7) and 10(-9) M. In contrast, alterations in surface antigen expression or suppression of proliferative responses did not occur in the mitogen-activated PBL over the whole concentration range of TCDD. These results clearly demonstrate that lymphoproliferation, as well as phenotypes of human PBL, are not affected by dioxin treatment and thus are not useful as sensitive biomarkers in human exposure studies.
与二噁英（2,3,7,8-四氯二苯并-对-二噁英，TCDD）在实验动物中已得到充分记录的免疫抑制作用相反，尽管已有报告指出，意外或职业性接触二噁英的人类出现了不良健康影响，但二噁英对人类免疫系统的影响仍存在争议。最近，有报告称，用低至10(-12)-10(-14)M TCDD的二噁英浓度进行体外处理后，丝裂原激活的人类外周血淋巴细胞（PBL）的特定亚群出现了剂量依赖性减少，这些亚群包括辅助诱导/记忆细胞（CD4+CD29+）和B细胞（CD20+）[1]。因此，对二噁英对人类PBL亚群的直接影响进行了更详细的研究，以评估用于人类二噁英暴露的敏感指标系统的可用性。用美洲商陆丝裂原（PWM）或抗CD3单克隆抗体（OKT3）刺激健康志愿者的PBL，并用10(-7)-10(-14)M TCDD处理3-4天。通过乙氧基-试卤灵-O-脱乙基酶（EROD）测定法测定细胞色素P450（CYP1A1）酶的诱导情况。通过流式细胞术分析不同淋巴细胞亚群的百分比，包括CD2（T细胞）、CD4、CD45 RA（抑制诱导/原始T细胞）、CD4、CD29、CD8、CD19（B细胞），以及白细胞介素2（IL-2）受体（CD25）和II类抗原（人类白细胞抗原HLA-DR）的表达。培养3-4天后，通过3H-胸腺嘧啶核苷摄取测定增殖活性。在本研究中，所有受刺激的淋巴细胞培养物在二噁英浓度为10(-7)和10(-9)M时均显示CYP1A1活性显著增加。相反，在整个TCDD浓度范围内，丝裂原激活的PBL中未出现表面抗原表达改变或增殖反应受抑制的情况。这些结果清楚地表明，淋巴细胞增殖以及人类PBL的表型不受二噁英处理的影响，因此在人类暴露研究中不能用作敏感的生物标志物。
