Cytokine Profiles In Asthma And Allergic Diseases

过敏性疾病，如哮喘、过敏性鼻炎和嗜酸性胃肠炎，是粘膜的炎症性疾病。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淋巴细胞进入粘膜，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。该项目旨在检测肥大细胞、嗜碱性粒细胞和T细胞亚群的细胞因子和介体分布，这些亚群可能参与过敏性疾病炎症的发生。我们已经开发了灵敏的细胞内细胞因子分析来测量过敏原特异性T细胞细胞因子的反应，而保真度到目前为止还不可能。使用这些方法，我们发现变应原特异性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。此外，这些产生细胞因子的Th2细胞的异质性表明，特定的疾病实体或炎症过程可能是产生不同细胞因子的Th2细胞优先分化的结果。过敏原特异性记忆T细胞的特定亚群已被鉴定，并正在对促进和抑制这些亚群的因素进行调查。在开发阻断这些细胞分化和功能的治疗方法的过程中，需要彻底了解这些亲过敏炎症T细胞的生物学特性。 此外，我们还扩展了我们之前对携带IgE受体(FceRI)的抗原提呈细胞的工作，并鉴定了表达FceRI的单核细胞亚群。此亚群的FceRI表达与血清IgE浓度相关，并可被治疗用抗IgE降低。这些结果进一步明确了FceRI和IgE在抗原提呈中的作用，并提示抗IgE药物可能通过这一机制影响变应原特异性T细胞的激活。

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.