EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON INTERLEUKIN-4-MEDIATED MECHANISMS OF IMMUNITY
EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON INTERLEUKIN-4-MEDIATED MECHANISMS OF IMMUNITY
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DOI：
10.1016/0378-4274(94)03185-a
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发表时间：
1995-01-01
影响因子：
3.5
通讯作者：
HOLSAPPLE, MP
中科院分区：
文献类型：
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作者：
KARRAS, JG;CONRAD, DH;HOLSAPPLE, MP
由于早期研究表明，多效性细胞因子白介素4(IL-4)和环境污染物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相似，我们研究了体外直接暴露于TCDD所介导的免疫抑制是否源于IL-4样生物活性。特别是，测试了TCDD模拟B细胞对IL-4的标志性反应的能力，如上调II型主要组织相容性复合体(MHC)抗原，增加细胞表面低亲和力形式的IgE受体(CD23)的表达，以及诱导免疫球蛋白类转换。在容易抑制B细胞增殖和抗体形成细胞反应的浓度下，TCDD未能显示出平行培养中观察到的任何IL-4活性。此外，在TCDD在加入IL-4之前与B细胞预先孵育的实验中，没有观察到IL-4活性增加的证据。相反，TCDD预先孵育导致B细胞培养中IgG1和IgE分泌减少，刺激B细胞通过与细菌脂多糖(LPS)和IL-4孵育进行免疫球蛋白类别转换。由于TCDD对单独脂多糖诱导的IgM分泌有类似的抑制作用(即不产生IL-4)，因此TCDD似乎抑制了能够分泌抗体的完全分化的B细胞的形成，而对类转换事件本身没有影响。再加上该实验室和其他实验室以前的报告，这些观察表明TCDD能够抑制几类免疫球蛋白的分泌。
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 IgGl 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.