AIRWAY FUNCTION--ROLE OF GAMMA DELTA T CELLS

气道功能--Gamma Delta T 细胞的作用

• 批准号: 6390841
• 负责人: WILLI K BORN
• 金额: $ 30.76万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390841
• 关键词: T cell receptor; T lymphocyte; carbohydrate receptor; genetically modified animals; glycosylation; interleukin 1; interleukin 10; interleukin 6; laboratory mouse; leukocyte activation /transformation; mannose; natural killer cells; ovalbumin; protein biosynthesis; receptor expression; receptor mediated endocytosis; respiratory epithelium; respiratory function; respiratory hypersensitivity; tissue /cell culture; tissue mosaicism; transforming growth factors; tumor necrosis factor alpha

DESCRIPTION: (Adapted from the Investigator's abstract): The broad, long-term objective of this application is to define the role of gamma delta T cells in the regulation of airway functions. This process is of vital importance during pulmonary infection, exposure to environmental pollutants, and allergic exposure in sensitized hosts, but the underlying mechanisms that maintain it are still poorly understood. The investigators have found that murine gamma delta T cells regulate airway tone during innate and allergic immune responses to the model allergen chicken ovalbumin (cOVA). They propose to characterize this newly discovered function of gamma delta T cells, to define how this process activates gamma delta T cells, and to investigate the mechanism of gamma delta T cell-dependent airway regulation. They hypothesize that cOVA is specifically recognized by airway phagocytes and endocytosed, which stimulates an innate response that in turn activates gamma delta T cells. Activated gamma delta T cells then modulate the innate response via a negative feedback mechanism, and thereby control the effect of this response of airway function, particularly airway tone. To test this, they will: 1. Determine which gamma delta T cells are responsible for the regulation of innate airway responses initiated by inhalation of nebulized cOVA. They will further document the critical role of local, pulmonary populations and identify TCR-defined subsets regulating airway tone. 2. Define how cOVA induces innate airway responses, including the initiation of gamma delta T cell regulatory function. 3. Identify the targets of gamma delta T cell regulation in the innate airway response to cOVA. They will delineate the targets of gamma delta T cell regulation, including the innate endocytic response of airway phagocytes, airway cytokine production, and airway epithelial cell function. 4. Compare gamma delta T cell regulatory functions in the innate airway response and in allergic airway hyper-responsiveness induced by cOVA. Two basic ideas will be tested, namely that gamma delta T cells functions are the same regardless of the mechanism of airway stimulation, and secondly, that gamma delta T cells specifically control antigen-specific alpha beta T cells during allergic airway hyper-responsiveness.

描述：(改编自《调查者摘要》)：广泛、长期 这项应用的目的是确定伽玛-德尔塔T细胞在 对呼吸道功能的调节。这一进程在以下方面至关重要 肺部感染、暴露于环境污染物和过敏 在致敏宿主中的暴露，但维持它的潜在机制 人们对此仍然知之甚少。研究人员发现，小鼠的伽马 DeltaT细胞在先天和变态反应性免疫反应中调节气道张力 模型过敏原鸡卵清蛋白(Cova)。他们建议将 这一新发现的伽马增量T细胞的功能，来定义这是如何 Process激活Gamma Delta T细胞，并探讨其作用机制 γ-增量T细胞依赖的呼吸道调节。他们假设科瓦是 被呼吸道吞噬细胞特异性识别并被内吞，刺激 这是一种先天反应，进而激活了伽马-德尔塔T细胞。活化伽马 然后，Delta T细胞通过负反馈调节先天反应 机制，从而控制这种呼吸道功能反应的效果， 尤其是呼吸道紧张感。为了测试这一点，他们将： 1.确定哪些伽马增量T细胞负责调节 雾化吸入Cova引起的先天呼吸道反应。他们会 进一步记录当地、肺部人口的关键作用，并确定 TCR定义的调节气道张力的子集。 2.明确Cova如何诱导先天呼吸道反应，包括启动 γ-增量T细胞调节功能。 3.天然呼吸道γ-βT细胞调节靶点的确定 对Cova的回应。他们将描绘出伽马三角洲T细胞的目标 调节，包括呼吸道吞噬细胞的固有内吞反应， 呼吸道细胞因子的产生和呼吸道上皮细胞的功能。 4.比较固有呼吸道中的Gamma-Delta T细胞调节功能 在Cova诱导的过敏性呼吸道高反应性中。两个基本要素 这种想法将得到检验，即伽马增量T细胞的功能是相同的 不管呼吸道刺激的机制是什么，其次，伽马 在这个过程中，Delta T细胞特异性地控制抗原特异性的α-βT细胞 过敏性呼吸道高反应性。