MECHANISMS OF T CELL MEDIATED LUNG INJURY

描述(根据申请者的抽象和具体目标改编)：t 淋巴细胞在多种人类肺部疾病中渗入肺部 以急性和慢性肺损伤为特征。其作用机制 导致肺损伤的潜在原因，以及由此对 肺部生理学仍不清楚。T细胞能够表达一种 多种效应器功能，包括直接细胞学活动 (利用至少两种不同的分子机制)以及 分泌一些可溶的炎症介质。很有可能 T细胞渗入肺导致实质细胞损伤 通过几种直接和间接的机制。这个项目的目标是 了解T细胞直接损伤T细胞的具体机制 肺，尤其是肺泡上皮细胞。这种伤害的影响 对呼吸生理学也将进行分析。具体目标是：1) 肺损伤类型和病理生理特征的研究 一系列由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 无论是在结构上，还是在生理上， 肺部的异常。2)体外培养体系的建立 T淋巴细胞与肺泡细胞的特异性相互作用分析 为了探索上皮细胞对抗原的处理能力 肺泡上皮细胞及CD8+T细胞参与的分子机制 细胞对上皮细胞的细胞毒性损伤。3)机制分析 CD8+T细胞在体内直接诱导肺损伤，通过一系列的 利用基因缺陷T细胞和 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.