Malaghan Institute of Medical Research, Box 7060, Wellington 6242, New Zealand.
J Immunol Methods. 2013 Aug 30;394(1-2):62-72. doi: 10.1016/j.jim.2013.05.004. Epub 2013 May 17.
Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease (Gavett et al., 1994). The development of the G4 mouse, that expresses green fluorescent protein (GFP) as a surrogate for IL-4 protein expression has made it possible to directly track the immune cells that produce IL-4. By combining a reliable intradermal immunisation technique with the transgenic G4 mouse we have been able to develop a novel & unique in vivo primary Th2 immune response model (PTh2). When allergens relevant to human disease are evaluated using the PTh2 assay a dose dependent hierarchy of allergenicity is revealed with environmental allergens (cockroach, house dust mite) the most potent and food allergens being the least. In addition, the PTh2 assay is extremely sensitive to the immunoregulatory effects of Mycobacterial extracts and immunosuppressive drugs on primary Th2 cell development. Taken together, this assay provides a standardised method for the identification of the structural and functional properties of proteins relevant to allergenicity, and is a powerful screening tool for novel lead compounds that are effective at inhibiting the primary Th2 response in allergic diseases.
过敏原的暴露,无论是人为的还是来自我们的环境,与人类健康问题如过敏和哮喘的发展越来越相关。过敏原诱导 Th2 细胞产生细胞因子白细胞介素(IL-)4,这是过敏疾病发病机制的核心(Gavett 等人,1994 年)。G4 小鼠的开发,通过表达绿色荧光蛋白(GFP)作为 IL-4 蛋白表达的替代物,使得直接跟踪产生 IL-4 的免疫细胞成为可能。通过将可靠的皮内免疫技术与转基因 G4 小鼠结合,我们已经能够开发出一种新型且独特的体内原发性 Th2 免疫反应模型(PTh2)。当使用 PTh2 测定法评估与人类疾病相关的过敏原时,会揭示出一种与环境过敏原(蟑螂、屋尘螨)相关的过敏原性的剂量依赖性层次结构,而食物过敏原则是最不有效的。此外,PTh2 测定法对分枝杆菌提取物和免疫抑制药物对原发性 Th2 细胞发育的免疫调节作用极其敏感。总之,该测定法为鉴定与过敏原性相关的蛋白质的结构和功能特性提供了一种标准化方法,并且是一种有效的筛选工具,可用于筛选可有效抑制过敏性疾病中原发性 Th2 反应的新型先导化合物。