LYMPHOKINE PROFILES IN ASTHMA AND ALLERGIC DISEASES

哮喘是一种呼吸道的炎症性疾病。 在过敏原暴露后，携带IgE的细胞，如肥大细胞和 嗜碱性粒细胞首先被激活。随后，T淋巴细胞进入 气道，被过敏原激活，并在调节 这种炎症反应通过细胞因子的产生 如IL-4、IL-5和IFN-γ。该项目旨在研究 肥大细胞、嗜碱性粒细胞和T细胞的细胞因子谱 亚群，可能参与产生 哮喘气道炎症。一个目标是识别肥大细胞 和嗜碱性粒细胞的产物，可能有助于支气管 炎症第二个目标是确定细胞因子谱， 外周血和支气管肺泡灌洗（BAL）T细胞来自 哮喘患者和正常志愿者，以确定是否真的有 产生特异性细胞因子的T细胞亚群的优先运输。 最后，我们希望表征人NK 1 T细胞，其在 小鼠变态反应模型在启动Th 2极化中起关键作用 T细胞反应。到目前为止，我们已经发现人类肥大细胞， 包括肺中的细胞，产生和分泌IL-16， CD 4 T细胞的趋化因子。IL-16占大多数 肥大细胞分泌的CD 4 T细胞趋化活性。这 T细胞向暴露于变应原的肺的运输已经被证实是一种免疫应答。 通过支气管肺泡灌洗检查，证明了主要的 Th 1配置文件。我们还发现了一种类似于 先前描述的鼠NK 1 T细胞，表征其独特的 TCR使用V-α-24、V-β-11。NK 1细胞表达IL-4， 相对于主流T细胞，T细胞水平高6倍， 在Th 0双重表达表型的细胞中唯一发现。 使用类似的技术，我们已经表明，嗜碱性粒细胞获得 是过敏性哮喘患者IL-4的主要来源， 外周血单个核细胞

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 profiles of mast cell, basophil and T cell subpopulations that may be involved in the generation of inflammation in asthmatic airways. One goal is to identify mast cell and basophil products that may contribute to bronchial inflammation. A second goal is to define the cytokine profile of peripheral blood and bronchoalveolar lavage (BAL) T cells from asthmatics and normal volunteers, to determine if indeed there is preferential trafficking of specific cytokine producing T cell subsets. Finally, we wish to characterize human NK1 T cells, which in mouse models of allergy play a key role in initiating Th2 polarized T cell responses. To date, we have found that human mast cells, including those in the lungs, produce and secrete IL-16, a chemotactic factor for CD4 T cells. IL-16 accounts for a majority of the CD4 T cell chemotactic activity secreted by mast cells. This trafficking of T cells to the allergen exposed lung has been examined by bronchoalveolar lavage, demonstrating a predominant Th1 profile. We have also identified a human analog of the previously described murine NK1 T cell, characterizing their unique TCR usage of V-alpha-24, V-beta-11. IL-4 was expressed in NK1 T cells at a 6 fold greater level relative to mainstream T cells and was uniquely found in cells of a Th0 dual expressing phenotype. Using similar techniques, we have shown that basophils obtained from allergic asthmatics are the predominant source of IL-4 in peripheral blood mononuclear cells.