Cytokine Profiles In Asthma And Allergic Diseases

哮喘是一种呼吸道炎症性疾病。过敏原暴露后，携带IgE的细胞，如肥大细胞和嗜碱性粒细胞，首先被激活。后来，T淋巴细胞进入呼吸道，被变应原激活，并通过IL-4、IL-5和干扰素-γ等细胞因子的分泌在调节这种炎症反应中发挥关键作用。本项目旨在研究肥大细胞、嗜碱性粒细胞和T细胞亚群的细胞因子和介体分布，这些亚群可能与哮喘呼吸道炎症的发生有关。我们已经开发出灵敏的细胞内细胞因子分析方法，几乎可以直接在体外测量过敏原特异性T细胞细胞因子反应。使用这些方法，我们已经证明了变应原特异性T细胞主要是典型的Th2表型，并且在单细胞水平上IL-4、IL-5和IL-13高度共表达。有趣的是，通常被认为是Th1细胞因子的IL-2也高度共表达。变应原特异性T细胞高水平表达CCR4和CRTH2趋化受体。这些结果提供了T细胞对过敏原反应的详细情况，而保真度到目前为止是不可能的。

Asthma is an inflammatory disease of the airways. After allergen exposure, IgE bearing cells, such as mast cells and basophils, are first activated. Later, T lymphocytes enter the airways, are activated by allergen and play a key role in regulating this inflammatory response through the elaboration of cytokines such as IL-4, IL-5 and IFN-gamma. This project seeks to examine the cytokine and mediator profiles of mast cell, basophil and T cell subpopulations that may be involved in the generation of inflammation in asthmatic airways. We have developed sensitive intracellular cytokine assays to measure allergen specific T cell cytokine responses almost directly ex vivo. Using these methods, we have shown that allergen specific T cells are predominantly of the classic Th2 phenotype and that on the single cell level IL-4, IL-5 and IL-13 are highly co-expressed. Interestingly, IL-2, which is often considered a Th1 cytokine was also highly coexpressed. Allergen specific T cell expressed high levels of the CCR4 and CRTH2 chemoattractant receptors. These results provide a detailed view of the T cell response to allergens with a fidelity heretofore not possible.