van Wijk F, Hartgring S, Koppelman S J, Pieters R, Knippels L M J
Institute for Risk Assessment Sciences, Immunotoxicology, Utrecht University, Utrecht, The Netherlands.
Clin Exp Allergy. 2004 Sep;34(9):1422-8. doi: 10.1111/j.1365-2222.2004.02062.x.
Peanut allergy is known for its severity and persistence through life. Several peanut proteins have been identified as allergenic and are indicated as Ara h 1-7. Very little is known about the mechanisms that underlie sensitization to peanut proteins.
The purpose of the present study was to reveal the immune responses that are induced against peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 during sensitization, including the very early responses.
Humoral and T cell responses against peanut and the peanut allergens were examined in an early and later stage of sensitization in an established murine model of peanut anaphylaxis. Therefore C3H/HeJ mice were orally exposed to two different doses of peanut extract plus cholera toxin.
Oral sensitization to peanut was characterized by an antigen-induced mixed cytokine response in the spleen (IL-4, IL-5, IL-10 and IFN-gamma), which could already be observed 7 days after the onset of exposure. Additionally, polyisotypic humoral responses (IgE, IgG1 and IgG2a) against peanut were found in the serum. Moreover, we demonstrated that these T helper (Th)1/Th2 cytokine and antibody responses were also directed specifically against the major peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6.
This study implicates that both Th1 and Th2 phenomena are involved in the development of peanut allergy in the C3H/HeJ murine model. Furthermore, we show that the present oral model is suitable to examine immune responses to food allergens during different stages of sensitization upon treatment with a whole food extract.
花生过敏以其严重程度和终身持续性而闻名。几种花生蛋白已被鉴定为过敏原,并被标记为Ara h 1 - 7。关于花生蛋白致敏的潜在机制知之甚少。
本研究的目的是揭示在致敏过程中针对花生以及花生过敏原Ara h 1、Ara h 2、Ara h 3和Ara h 6诱导的免疫反应,包括非常早期的反应。
在已建立的花生过敏小鼠模型中,在致敏的早期和后期检查针对花生和花生过敏原的体液和T细胞反应。因此,将C3H/HeJ小鼠口服给予两种不同剂量的花生提取物加霍乱毒素。
口服花生致敏的特征是脾脏中抗原诱导的混合细胞因子反应(IL - 4、IL - 5、IL - 10和IFN - γ),在接触开始后7天就可以观察到。此外,在血清中发现了针对花生的多亚型体液反应(IgE、IgG1和IgG2a)。此外,我们证明这些T辅助(Th)1/Th2细胞因子和抗体反应也特异性地针对主要花生过敏原Ara h 1、Ara h 2、Ara h 3和Ara h 6。
本研究表明,Th1和Th2现象都参与了C3H/HeJ小鼠模型中花生过敏的发展。此外,我们表明目前的口服模型适用于在用全食物提取物治疗时检查致敏不同阶段对食物过敏原的免疫反应。