Dearman R J, Ramdin L S, Basketter D A, Kimber I
Zeneca Central Toxicology Laboratory, Macclesfield, U.K.
Immunology. 1994 Apr;81(4):551-7.
It has been demonstrated previously that chemical contact and respiratory allergens differ with respect to the quality of immune responses they will provoke in mice. Trimellitic anhydride (TMA), a human respiratory allergen, induces in mice responses consistent with the preferential activation of Th2-type cells, resulting in the production of IgE anti-hapten antibody and an increase in the serum concentration of IgE. In contrast, oxazolone (OX), a potent contact allergen considered not to cause respiratory hypersensitivity, induces instead Th1-type responses in mice characterized by vigorous IgG2a antibody production and a failure to elicit IgE. In the present study we have extended these investigations and have examined the capacity of these chemicals to stimulate inducible interleukin-4 (IL-4) production by draining lymph node cells (LNC). IL-4 was measured in the supernatants of draining LNC cultured for various periods in the presence or absence of concanavalin A (Con A). Following primary topical exposure to the chemical allergens, Con A-stimulated LNC from OX-treated mice secreted significantly more IL-4 than did LNC from mice exposed to trimellitic anhydride (TMA). A different pattern of IL-4 secretion was observed following culture with Con A of LNC prepared from lymph nodes draining the sites of secondary exposure to these chemicals. In this case significantly higher concentrations of IL-4 were produced by TMA-treated mice. Detectable levels of IL-4 (> 300 pg/ml) were not found following culture of draining LNC from sensitized mice in the absence of Con A or following culture of LNC from naive mice with or without Con A. These data demonstrate that chemical allergens of different types stimulate discrete and changing patterns of inducible IL-4 synthesis consistent with the selective activation of Th-cell subpopulations.
先前已经证明,化学接触性变应原和呼吸道变应原在引发小鼠免疫反应的性质方面存在差异。偏苯三酸酐(TMA)是一种人类呼吸道变应原,在小鼠中诱导的反应与Th2型细胞的优先激活一致,导致产生IgE抗半抗原抗体并使血清IgE浓度增加。相比之下,恶唑酮(OX)是一种强效接触性变应原,被认为不会引起呼吸道超敏反应,反而在小鼠中诱导以大量产生IgG2a抗体和无法引发IgE为特征的Th1型反应。在本研究中,我们扩展了这些研究,并检查了这些化学物质刺激引流淋巴结细胞(LNC)产生诱导性白细胞介素-4(IL-4)的能力。在有或没有伴刀豆球蛋白A(Con A)的情况下,在不同时间段培养引流LNC的上清液中测量IL-4。在初次局部暴露于化学变应原后,来自经OX处理的小鼠的Con A刺激的LNC分泌的IL-4明显多于暴露于偏苯三酸酐(TMA)的小鼠的LNC。在用Con A培养从二次暴露于这些化学物质的部位引流的淋巴结制备的LNC后,观察到不同的IL-4分泌模式。在这种情况下,经TMA处理的小鼠产生的IL-4浓度明显更高。在没有Con A的情况下培养致敏小鼠的引流LNC后,或在培养有或没有Con A的未接触过抗原的小鼠的LNC后,未发现可检测水平的IL-4(> 300 pg/ml)。这些数据表明,不同类型的化学变应原刺激与Th细胞亚群的选择性激活一致的离散且不断变化的诱导性IL-4合成模式。