REGULATION OF TH2 EFFECTOR FUNCTION IN THE AIRWAY

气道中 TH2 效应器功能的调节

• 批准号: 6273163
• 负责人: KIM BOTTOMLY
• 金额: $ 16.07万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273163
• 关键词: T cell receptor; asthma; cell cell interaction; cell transplantation; cellular immunity; cytokine receptors; genetically modified animals; helper T lymphocyte; inflammation; interleukin 4; interleukin 5; laboratory mouse; leukocyte activation /transformation; respiratory hypersensitivity

Asthma is a disease characterized by reversible airflow obstruction and bronchial inflammation. There is considerable evidence in human and murine models of asthma that CD4 T cells and in particular IL-4 and IL-5 secreting Th2 cells are associated with the characteristic airway response. The goals of this proposal are 1) to understand the role of committed Th1 and Th2 effector CD4 T cells in eliciting airway inflammation and bronchial hyperresponsiveness focussing on characterizing the unique pathology induced by each type of effector T cell and 2) to determine if the interaction between Th1 and Th2 cells in the airway is synergistic or antagonistic in the induction of airway events. To understand how the pathology associated with asthma can be elicited and regulated by activated CD4 T cells, we will take advantage of an established cell transfer system in which antigen-specific, committed Th1 cells, Th2 cells or both, derived from mice transgenic for a known T cell receptor, are transferred into naive mice and are recruited and activated in the airway by inhaled antigen. The role of Th1 and Th2 effector cells in inhibiting or exacerbating airway inflammation and hyperresponsiveness will be examined by 1) characterizing the effect of transferring either primed Th1 or Th2 CD4 effector T cells on airway events, 2) determining the role of Th2/Th1 cytokines and cytokine responsive cells in the generation of airway inflammation and AHR using cytokine/cytokine receptor deficient mice, and 3) determining the effect of Th1: Th2 interaction of the airway microenvironment on modulating the airway response elicited by a particular subset of CD4 T cell. From these studies we hope to gain an understanding of the role of Th1 and Th2 cells in eliciting a pathology characteristic of human asthma and to investigate methods to abrogate an ongoing, committed CD4 effector T cell response.

哮喘是一种以可逆性气流阻塞为特征的疾病 支气管炎症。 有大量证据表明人类和 CD4 T 细胞，特别是 IL-4 和 IL-5 的小鼠哮喘模型 分泌 Th2 细胞与特征性气道相关 回复。 该提案的目标是 1) 了解 诱导气道中的定型 Th1 和 Th2 效应 CD4 T 细胞 炎症和支气管高反应性集中于 表征每种效应 T 诱导的独特病理学 细胞和 2) 确定 Th1 和 Th2 细胞之间的相互作用是否 气道在气道诱导中是协同作用还是拮抗作用 事件。 了解如何得出与哮喘相关的病理学 并由激活的 CD4 T 细胞调节，我们将利用 建立了细胞转移系统，其中抗原特异性、定向 Th1 细胞、Th2 细胞或两者，源自已知 T 基因转基因小鼠 细胞受体，被转移到幼稚小鼠体内并被招募和 被吸入的抗原在气道中激活。 Th1和Th2的作用 效应细胞抑制或加剧气道炎症 超反应性将通过以下方式进行检查：1）表征 在气道上转移已引发的 Th1 或 Th2 CD4 效应 T 细胞 事件，2）确定Th2/Th1细胞因子和细胞因子的作用 反应细胞在气道炎症和 AHR 的产生中使用 细胞因子/细胞因子受体缺陷小鼠，以及 3) 确定效果 Th1: Th2 气道微环境相互作用对调节的影响 由 CD4 T 细胞的特定亚群引发的气道反应。 从 这些研究我们希望了解 Th1 和 Th2 细胞引发人类哮喘的病理特征并 研究消除持续、持续的 CD4 效应 T 的方法 细胞反应。