T-Lymphocytes, Latent Virus and Emphysema Pathogenesis

描述（由申请人提供）： 最近的数据表明，潜伏的腺病毒感染可能会上调 炎症过程中的肺，并在肺气肿的一个重要的辅助因素 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气道以及肺实质 肺部疾病 因此，有人假设， 慢性阻塞性肺疾病患者的细胞毒性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以下疾病的易感性显著增加： 肺气肿 此外，在这个早熟的过程中肺气肿的存在 与支气管上细胞毒性淋巴细胞数量增加有关， 肺泡灌洗 以此为背景， 目前的研究认为，CTL代表了对潜伏病毒感染的应答， 肺和直接有助于肺气肿的发病机制，通过加速 肺实质细胞凋亡。 为了解决这个问题，我们 检查使用从国家登记的受试者获得的肺组织 接受肺减容手术（LVRS）的肺气肿治疗试验。 本提案的具体目标是： 具体目标1：确定潜伏病毒感染与 患者肺上皮细胞、CTL浸润和程序性细胞死亡 晚期肺气肿 具体目的2：确定是否潜伏病毒感染肺泡 上皮细胞预测LVRS后肺气肿的进展。 总之，我们相信，该项目的成功完成将 为我们提供了关于潜伏病毒 感染，炎症反应的上调和 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.