Lang D S, Becker S, Clark G C, Devlin R B, Koren H S
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill.
Arch Toxicol. 1994;68(5):296-302. doi: 10.1007/s002040050072.
A wide variety of immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals has been documented. In contrast, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans after occupational or accidental exposure to dioxin. Recently, Neubert et al. (1991) found that a dose-dependent decrease of peripheral blood lymphocyte (PBL) subpopulations in humans and non-human primates, including helper-inducer/memory cells (CD4+CD29+) and B cells (CD20+) occurred in pokeweed mitogen (PWM) stimulated cultures at concentrations as low as 10(-12)-10(-14) M TCDD. Therefore, the direct effects of dioxin on human PBL subpopulations have been studied, in order to determine their usefulness as sensitive biomarkers for human dioxin exposure. Lymphocyte cultures from healthy individuals were treated with 10(-7) M-10(-14) M TCDD in the absence and presence of stimulation with pokeweed mitogen (PWM) or anti-CD3 monoclonal antibody (moAb; OKT3) for 3 days. Cytochrome P450 (CYP1A1) enzyme induction, one of the best studied direct biological effects of TCDD on numerous cell types, was assayed in parallel by ethoxyresorufin-O-deethylase (EROD) activity. 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 (HLA-DR) expression, were analyzed by flow cytometry. DNA synthesis was determined by 3H-thymidine uptake after 3 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
2,3,7,8-四氯二苯并-对-二噁英（TCDD）在实验动物中具有多种免疫抑制作用，这已得到证实。相比之下，二噁英对人类免疫系统的影响仍存在争议，尽管职业性或意外接触二噁英后已报告了对人类的不良健康影响。最近，诺伊贝特等人（1991年）发现，在低至10（-12）-10（-14）M TCDD浓度的商陆有丝分裂原（PWM）刺激培养物中，人类和非人类灵长类动物外周血淋巴细胞（PBL）亚群出现剂量依赖性减少，包括辅助诱导/记忆细胞（CD4 + CD29 +）和B细胞（CD20 +）。因此，研究了二噁英对人类PBL亚群的直接影响，以确定它们作为人类二噁英暴露敏感生物标志物的实用性。在有无商陆有丝分裂原（PWM）或抗CD3单克隆抗体（moAb；OKT3）刺激的情况下，用10（-7）M - 10（-14）M TCDD处理健康个体的淋巴细胞培养物3天。通过乙氧基试卤灵-O-脱乙基酶（EROD）活性平行测定细胞色素P450（CYP1A1）酶诱导，这是TCDD对多种细胞类型研究得最好的直接生物学效应之一。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（HLA-DR）表达。培养3天后，通过3H-胸腺嘧啶摄取测定DNA合成。（摘要截短于250字）
