MECHANISMS OF T CELL MEDIATED LUNG INJURY

描述（根据申请人的摘要和具体目标改编）：T 淋巴细胞在多种人类肺部疾病中浸润肺部， 以急性和慢性肺损伤为特征。 的机制 潜在的诱导肺损伤，以及由此产生的影响， 肺生理学仍不清楚。 T细胞能够表达 多种效应子功能，包括直接细胞学活性 （利用至少两种不同的分子机制）以及 分泌大量可溶性炎症介质。 很可能 肺的T细胞浸润导致实质细胞损伤 通过多种直接和间接的机制。 该项目的目标是 了解T细胞直接损伤细胞的具体机制。 肺，特别是肺泡上皮细胞。 这次受伤的影响 对呼吸生理学的影响也将进行分析。 具体目标是：1） 肺损伤模式和病理生理学特征的表征 在一系列研究中，CD8+T细胞引起的肺泡损伤的后果， 体内过继转移实验。 T细胞介导的损伤将是 在结构和生理方面都有特点， 肺的异常。 2)体外系统的开发 T淋巴细胞与肺泡上皮细胞特异性相互作用的分析 上皮细胞，以探测抗原处理能力， 肺泡上皮细胞，以及CD8+T细胞参与的分子机制， 上皮细胞的细胞毒性损伤。 3)机制分析 CD8+T细胞通过其直接诱导体内肺损伤， 利用遗传缺陷T细胞的过继转移实验， 受体小鼠

DESCRIPTION (Adapted from applicant's abstract and specific aims): T lymphocytes infiltrate the lung in a variety of human lung diseases which are characterized by acute and chronic lung injury. The mechanisms underlying the induction of injury to the lung, and the resultant impact on pulmonary physiology remain obscure. T cells are capable of expressing a variety of effector functions, including direct cytologic activity (utilizing at least two distinct molecular mechanisms) as well as the secretion of a number of soluble mediators of inflammation. It is likely that T cell infiltration of the lung results in damage to parenchymal cells by several direct and indirect mechanisms. The goal of this project is to understand the specific mechanisms by which T cells directly injure the lung, particularly the alveolar epithelial cell. The impact of this injury on respiratory physiology will also be analyzed. The specific aims are: 1) Characterization of the pattern of lung injury and the pathophysiologic consequences of alveolar injury produced by CD8+T cells, in a series of in vivo adoptive transfer experiments. T cell-mediated injury will be characterized both in terms of structural, as well as physiologic, abnormalities of the lung. 2) The development of an in vitro system for analysis of specific interactions between T lymphocytes and alveolar epithelial cells in order to probe the antigen processing capabilities of alveolar epithelial cells, and the molecular mechanisms involved in CD8+T cell cytotoxic injury to epithelial cells. 3) An analysis of the mechanisms by which CD8+T cells directly induce lung injury in vivo, with a series of adoptive transfer experiments utilizing genetically deficient T cells and recipient mice.