Dearman R J, Basketter D A, Kimber I
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK.
Immunology. 1995 Dec;86(4):545-50.
It has been demonstrated previously that a selective pattern of mitogen-inducible interleukin-4 (IL-4) production becomes apparent in mice after temporal evolution of the immune response to different classes of chemical allergen. Mitogen-stimulated draining lymph node cells (LNC) isolated after primary exposure to both the respiratory allergen trimellitic anhydride (TMA) and oxazolone, a contact allergen, secreted similar amounts of IL-4. Following secondary exposure, however, TMA, but not oxazolone, caused a marked increase in IL-4 production, consistent with the stimulation by TMA of a T-helper type-2 (Th2)-type response. In the present study, cytokine production characteristic of Th1 (interferon-gamma; IFN-gamma) and Th2 (IL-4 and IL-10) cell activation was examined following chronic exposure of mice to allergen over a 13-day period. In accord with previous studies, chronic exposure to TMA, but not to oxazolone, resulted in a substantial potentiation of mitogen-inducible IL-4 secretion. In addition, spontaneous IL-10 production by TMA-activated LNC was significantly higher than by cells prepared from oxazolone-exposed animals. The lower levels of Il-4 and IL-10 elaborated by oxazolone-activated LNC were not attributable to a reduced potential to secrete cytokine per se, as significantly more IFN-gamma was produced compared with TMA-activated LNC. It is proposed that these divergent cytokine production patterns reflect the selective stimulation of Th1- and Th2-type responses by contact and respiratory chemical allergens.
先前已经证明,在对不同种类化学变应原的免疫反应随时间演变后,小鼠中丝裂原诱导的白细胞介素-4(IL-4)产生的选择性模式变得明显。在初次暴露于呼吸道变应原偏苯三酸酐(TMA)和接触性变应原恶唑酮后分离得到的丝裂原刺激的引流淋巴结细胞(LNC)分泌相似量的IL-4。然而,二次暴露后,TMA而非恶唑酮导致IL-4产生显著增加,这与TMA对2型辅助性T细胞(Th2)型反应的刺激一致。在本研究中,在13天的时间里让小鼠长期暴露于变应原后,检测了Th1(干扰素-γ;IFN-γ)和Th2(IL-4和IL-10)细胞活化的细胞因子产生特征。与先前的研究一致,长期暴露于TMA而非恶唑酮导致丝裂原诱导的IL-4分泌大幅增强。此外,TMA激活的LNC自发产生的IL-10显著高于恶唑酮暴露动物制备的细胞。恶唑酮激活的LNC产生的较低水平的IL-4和IL-10并非归因于其本身分泌细胞因子的能力降低,因为与TMA激活的LNC相比,其产生的IFN-γ明显更多。有人提出,这些不同的细胞因子产生模式反映了接触性和呼吸道化学变应原对Th1型和Th2型反应的选择性刺激。