Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine production in ovalbumin (OVA)-immunized C57Bl/6 mice

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine production in ovalbumin (OVA)-immunized C57Bl/6 mice
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DOI:
10.1016/s0300-483x(01)00582-0
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发表时间:
2002-03-05
期刊:
影响因子:
4.5
通讯作者:
Tohyama, C
Tohyama, C
中科院分区:
医学3区
文献类型:
--
作者:
Nohara, K;Fujimaki, H;Tohyama, C

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已知2,3,7,8-四氯二苯并-对-二恶英(TCDD)抑制细胞和体液免疫。效应T细胞衍生的2型细胞因子。包括IL-4和IL-5,在体液免疫中起关键作用。在此,我们研究了TCDD是否影响免疫应答过程中2型细胞因子的产生。C57 B1/6小鼠用卵清蛋白(OVA)腹腔内免疫,并在第0天口服5或20 μ g TCDD/kg,然后在第21天用OVA攻击。7天后(第28天),研究了血浆中的抗原特异性抗体和脾细胞产生的T细胞衍生的细胞因子以及用OVA离体再刺激后脾细胞的增殖。血浆中IgM类和IgG 1类OVA特异性抗体的量分别减少5或20 μ g TCDD/kg和20 μ g TCDD/kg。当胸腺重量和细胞结构被20 μ g TCDD/kg降低时,脾脏重量和细胞结构没有被5或20 μ g TCDD/kg改变。脾脏中B和T细胞的比例不受TCDD暴露的影响。从另一方面来说。用5或20 μ g TCDD/kg处理的小鼠的脾细胞在用OVA离体再刺激后产生较少的IL-4或IL-5。T细胞生长因子IL-2的产生也减少了TCDD处理小鼠的脾细胞。相反。1型细胞因子IFN-γ被TCDD增加。20微克TCDD/kg可抑制卵清蛋白或T细胞有丝分裂原(Con A)刺激的脾细胞增殖,但不影响B细胞有丝分裂原(LPS)刺激的增殖。这些结果表明,受损的T细胞活化和抑制2型细胞因子的T细胞参与与TCDD暴露相关的体液免疫受损。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress both cellular and humoral immunity. Effector T cell-derived type-2 cytokines. including IL-4 and IL-5, play pivotal roles in humoral immunity. Herein, we studied whether TCDD affects type-2 cytokine productions during the immune response. C57B1/6 mice were intraperitoneally immunized with ovalbumin (OVA) and orally administered 5 or 20 mug TCDD/kg on Day 0, and then challenged with OVA on Day 21. Seven days later (Day 28), antigen-specific antibodies in plasma, and T cell-derived cytokines produced by splenocytes and proliferation of splenocytes upon ex vivo re-stimulation with OVA were investigated, The quantities of IgM class and IgG1 class OVA-specific antibodies in plasma were reduced by 5 or 20 mug TCDD/kg and by 20 mug TCDD/kg, respectively. While thymus weight and cellularity were reduced by 20 mug TCDD/kg, spleen weight and cellularity were not changed by either 5 or 20 mug TCDD/kg. The proportions of B and T cells in the spleen were not affected by TCDD exposure. On the other hand. splenocytes from mice treated with 5 or 20 mug TCDD/kg were shown to produce less IL-4 or IL-5 upon ex vivo re-stimulation with OVA. Production of the T cell growth factor IL-2 was also decreased in splenocytes from TCDD-treated mice. In contrast. the type-1 cytokine IFN-gamma was increased by TCDD. Twenty micrograms of TCDD/kg suppressed OVA- or T cell mitogen (Con A)-stimulated proliferation of splenocytes, but did not affect B cell mitogen (LPS)-stimulated proliferation. These results suggested compromised T cell activation and suppressed type-2 cytokine production by T cells to be involved in the impaired humoral immunity associated with TCDD exposure. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.