Cytokine Profiles In Asthma And Allergic Diseases

过敏性疾病，如哮喘、变应性鼻炎和嗜酸性胃肠炎，都是粘膜的炎症性疾病。在接触过敏原后，携带IgE的细胞，如肥大细胞和嗜碱性细胞，首先被激活。随后，T淋巴细胞进入粘膜，被过敏原激活，并通过IL-4、IL-5、ifn - γ等细胞因子的调控，在炎症反应中发挥关键作用。本项目旨在研究肥大细胞、嗜碱性细胞和T细胞亚群中可能参与过敏性疾病炎症产生的细胞因子和介质谱。我们已经开发了敏感的细胞内细胞因子测定，以测量过敏原特异性T细胞细胞因子反应的保真度，迄今为止是不可能的。使用这些方法，我们已经证明过敏原特异性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。此外，这些产生Th2细胞的细胞因子的异质性一直存在，这表明特定疾病实体或炎症过程可能是不同产生Th2细胞因子的细胞优先分化的结果。已经确定了过敏原特异性记忆T细胞的特定亚群，并正在研究促进和抑制这些亚群的因素。全面了解这些促过敏炎性T细胞的生物学特性是开发阻断这些细胞分化和功能的治疗方法的第一步。

Allergic diseases, such as asthma, allergic rhinitis and eosinophilic gastroenteritis, are inflammatory diseases of the mucosa. After allergen exposure, IgE bearing cells, such as mast cells and basophils, are first activated. Later, T lymphocytes enter the mucosa, 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 allergic diseases. We have developed sensitive intracellular cytokine assays to measure allergen specific T cell cytokine responses with a fidelity heretofore not possible. 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. Furthermore, heterogeneity of these cytokine producing Th2 cells has been, suggesting the possibility that specific diseases entities or inflammatory processes are the result of preferential differentiation of distinct cytokine producing Th2 cells. Specific subsets of allergen specific memory T cells have be identified and investigations into the factors promoting and inhibiting these subsets are being made. A thorough understanding of the biology of these pro-allergic inflammatory T cells is needed as a step in the development of therapeutic approaches to blocking the differentiation and function of these cells. Additionally, we have extended our previous work with IgE receptor (FceRI) bearing antigen presenting cells and have identified a subset of monocytes that express FceRI. FceRI expression by this subset correlated to serum IgE concentration and was reduced by therapeutic administration of anti-IgE. These results further define the role of FceRI and IgE in antigen presentation, and suggest that via this mechanism, anti-IgE therpeutics may have an effect on allergen specific T cell activation.