HUMORAL AND CELL-MEDIATED IMMUNITY IN DEVELOPMENT OF BRONCHIAL HYPERRESPONSIVE

支气管高反应性发展中的体液和细胞介导的免疫

• 批准号: 3736561
• 负责人: ERWIN W GELFAND
• 金额: --
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736561
• 关键词: T cell receptor; asthma; athymic mouse; cellular immunity; disease /disorder model; histopathology; humoral immunity; immunoglobulin E; inflammation; laboratory mouse; plethysmography; respiratory airflow disorder; species difference; tissue /cell culture

Asthma is a disease of the airways, where most patients demonstrate bronchial hyperresponsiveness (BHR) to a range of triggers including drugs such as methacholine. Asthma is most often associated with airway inflammation but the evidence associating asthma with inflammation, albeit compelling, is circumstantial. The long term objectives of this project are to delineate the role of humoral and cell-mediated immunity in the development of BHR, especially the role of IgE antibody and specific T- lymphocyte subsets. Knowledge of the murine immune system, its functional compartmentalization and defined genetic differences in the ability to generate IgE antibodies offers distinct advantages for using this species over other animal models of BHR. We have now developed an experimental model of BHR in mice following exposure to inhaled antigen. In the absence of adjuvant, BALB/c mice develop a brisk IgE antibody response associated with a marked increase in the peri-bronchial associated lymph nodes (PBLN) and numbers of antigen-reactive T cells. Moreover using in vivo (body plethysmography) and in vitro (tracheal smooth muscle contraction) assays, we demonstrate that mice sensitized by inhalation of antigen develop BHR. In this project we will determine the role of local and systemic immunity in the pathogenesis of BHR. We will study the development of BHR in high and low IgE responding mice, in athymic (nude) mice, as well as following adoptive transfer of distinct lymphocyte subsets from previously sensitized animals or antigen-specific T-cell clones of different phenotypes. We will directly delineate the role for IgE antibody in passive transfer experiments as well as determining whether T-cell receptor Vbeta usage is restricted in sensitized or IgE-producing animals. These studies will provide new and important information concerning the role of T-B interactions and IgE in the pathogenesis of BHR.

哮喘是一种呼吸道疾病，大多数患者都有这种症状