T-Lymphocytes, Latent Virus and Emphysema Pathogenesis

描述(由申请人提供)： 最近的数据表明，潜伏性腺病毒感染可能上调 肺内炎症过程，是肺气肿的重要辅助因素 发展。此外，最近的肺活检研究表明， 肺淋巴细胞，特别是CD8+细胞更常见于 慢性阻塞性肺疾病患者的呼吸道和肺实质 肺部疾病。因此，人们假设淋巴细胞与 以慢性阻塞性肺疾病为代表的细胞毒性T淋巴细胞 (CTL)对潜伏病毒的反应。支持这一假设的是数据 表明感染艾滋病毒的吸烟者对 肺气肿。此外，肺气肿的出现在这种早熟过程中 与支气管上细胞毒性淋巴细胞数量的增加有关 肺泡灌洗。以此为背景， 目前的研究表明，CTL是对潜伏的病毒感染的一种反应 通过加速肺气肿的发生，直接参与肺气肿的发病 肺实质细胞凋亡性死亡。为了解决这一假设，我们 使用从国家注册受试者获得的肺组织进行检查 接受肺减容手术(LVRS)的肺气肿治疗试验。 目前这项建议的具体目标是： 具体目标1：确定潜伏病毒感染之间的关系 肺上皮细胞、CTL浸润和程序性细胞死亡 患有晚期肺气肿。 特定目的2：确定肺泡潜伏病毒感染 上皮细胞可预测肺减容术后肺气肿的进展。 最后，我们相信，这一项目的圆满完成将 为我们提供了关于潜伏病毒作用的非常重要的信息 感染、炎症反应上调及其发病机制的研究进展 肺气肿。

DESCRIPTION (provided by applicant): Recent data has suggested that latent adenoviral infections may up-regulate inflammatory processes in the lung and be an important co-factor in emphysema development. In addition recent lung biopsy studies have demonstrated that lung lymphocytes, particularly CD8+ cells are found more commonly in the airway as well as the lung parenchyma in individuals with chronic obstructive pulmonary disease. It has thus been hypothesized that lymphocytes associated with chronic obstructive pulmonary disease represent a cytotoxic T-lymphocyte (CTL) response to latent virus. In support of this hypothesis is data demonstrating a marked increased susceptibility of HIV infected smokers to emphysema. Furthermore, the presence of emphysema in this precocious process is associated with increased numbers of cytotoxic lymphocytes on broncho- alveolar lavage. With this as a background, the central hypothesis of the present study is that CTL's represent a response to latent viral infection in the lung and contribute directly to emphysema pathogenesis by accelerating apoptotic cell death of lung parenchyma. To address this hypothesis, we examine use lung tissue obtained from subjects enrolled in the National Emphysema Treatment Trial undergoing lung volume reduction surgery (LVRS). The specific aims of the current proposal are: Specific Aim 1: To determine the relationship between latent virus infection of lung epithelium, CTL infiltration and programmed cell death in patients with advanced emphysema. Specific Aim 2: To determine whether latent viral infection of alveolar epithelium predicts progression of emphysema following LVRS. In conclusion, we believe that successful completion of this project will provide us with very important information regarding the role of latent viral infection, upregulation of the inflammatory response and the pathogenesis of emphysema.