Karras J G, Conrad D H, Holsapple M P
Department of Pharmacology, Medical College of Virginia/Virginia Commonwealth University, Richmond.
Toxicol Lett. 1995 Jan;75(1-3):225-33. doi: 10.1016/0378-4274(94)03185-a.
Because of similarities in the independent actions of the pleiotropic cytokine, interleukin-4 (IL-4), and the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on murine B-lymphocytes suggested in earlier studies, we have investigated whether the immunosuppression mediated by direct exposure to TCDD in vitro is due to an IL-4-like biological activity. In particular, the ability of TCDD to mimic hallmark responses of B-cells to IL-4, such as upregulation of major histocompatibility complex (MHC) antigens of the class II type, increases in cell surface expression of the low affinity form of the Fc receptor for IgE (CD23) and induction of immunoglobulin class switching, was tested. At concentrations that readily suppress B-cell proliferative and antibody-forming cell responses, TCDD failed to demonstrate any of the activities of IL-4 observed in parallel cultures. Further, in experiments in which TCDD was preincubated with B-cells before addition of IL-4, no evidence of increased IL-4 activity was observed. Rather, TCDD preincubation resulted in decreased secretion of IgG1 and IgE in B-cell cultures stimulated to undergo immunoglobulin class switching by incubation with bacterial lipopolysaccharide (LPS) and IL-4. Because TCDD produced comparable suppression of IgM secretion induced by LPS alone (i.e., no IL-4), it appears that TCDD inhibits the formation of fully differentiated B-cells capable of secreting antibody and has no effects on class switching events per se. Coupled with previous reports from this and other laboratories, these observations indicate that TCDD is able to suppress secretion of several classes of immunoglobulin.
由于早期研究表明多效性细胞因子白细胞介素-4（IL-4）与环境污染物2,3,7,8-四氯二苯并对二恶英（TCDD）对小鼠B淋巴细胞的独立作用存在相似性，我们研究了体外直接暴露于TCDD介导的免疫抑制是否归因于类似IL-4的生物活性。特别是，测试了TCDD模拟B细胞对IL-4标志性反应的能力，如II类主要组织相容性复合体（MHC）抗原的上调、IgE低亲和力形式的Fc受体（CD23）细胞表面表达的增加以及免疫球蛋白类别转换的诱导。在易于抑制B细胞增殖和抗体形成细胞反应的浓度下，TCDD未能在平行培养物中表现出IL-4的任何活性。此外，在添加IL-4之前将TCDD与B细胞预孵育的实验中，未观察到IL-4活性增加的证据。相反，TCDD预孵育导致在与细菌脂多糖（LPS）和IL-4孵育以诱导免疫球蛋白类别转换的B细胞培养物中IgG1和IgE的分泌减少。由于TCDD对单独由LPS诱导的IgM分泌（即无IL-4）产生了相当的抑制作用，似乎TCDD抑制了能够分泌抗体的完全分化B细胞的形成，并且对类别转换事件本身没有影响。结合本实验室和其他实验室以前的报告，这些观察结果表明TCDD能够抑制几类免疫球蛋白的分泌。
