CYTOMEGALOVIRUS PNEUMONITIS DURING GRAFT VS HOST DISEASE

虽然巨细胞病毒(CMV)所致的间质性肺炎是 免疫功能低下患者的主要发病率来源，很少 已知巨细胞病毒间质性肺炎的发病机制 病毒和宿主因素在本病发生中的相对贡献 进程。 我们先前观察到小鼠巨细胞病毒(MCMV)感染显著 增强GVH对主要组织相容性抗原(HA)和Lead的反应 对重症间质性肺炎，不能单独用病毒或GVH。 初步数据显示，合并MCMV/GVH的肺炎是 而不是由于GVH导致肺部病毒复制增加所致。 这项建议的目的是确定病毒和宿主的免疫 巨细胞病毒间质性肺炎发病机制的重要因素 与生殖器疱疹相关。我们将研究病毒复制在 肺炎的发生和支持MCMV的肺结构的确定 用原位杂交方法进行复制。我们还将研究 巨细胞病毒肺复制与GVH及间质的定量关系 肺炎，通过使用抗病毒药物调节肺部的病毒复制 制剂、疫苗接种和巨细胞病毒突变体。我们还将确定MCMV是否 在肺炎期间出现，病毒不能通过培养恢复 肺组织匀浆。 GVH/MCMV期间宿主免疫过程在肺中的作用 间质性肺炎也将被检查。我们将描述 发生在肺部的细胞变化，决定了淋巴细胞 细胞的表型和来源(供体/受体) 阿龙。我们还将检查在中运行的功能CMI流程 肺，并确定这些基因是针对MCMV还是针对宿主H2决定因素。 通过免疫组织化学方法，我们将检查在 肺炎时H2抗原在肺组织中的表达我们还将 确定宿主免疫反应的修改是否会改变 间质性肺炎。 最后，我们将确定GVH到次要HA是否会改变MCMV复制 在肺部或导致间质性肺炎。这些研究应该 大大提高我们对巨细胞病毒致病机理的认识 肺炎以及病毒和宿主因素的相互作用，可能是 与疾病的起源有关。

Although interstitial pneumonitis due to cytomegalovirus (CMV) is a significant source of morbidity for the immunocompromised patient, little is known about the pathogenesis of CMV interstitial pneumonitis and the relative contributions of virus and host factors to the genesis of this process. We previously observed that murine CMV (MCMV) infection significantly augments GVH reaction to major histocompatibility antigens (HA) and leads to severe interstitial pneumonitis, not seen with virus or GVH alone. Preliminary data indicates that pneumonitis seen in combined MCMV/GVH is not the consequence of increased virus replication in the lung due to GVH. The objective of this proposal is to determine the viral and host immune factors important in the pathogenesis of MCMV interstitial pneumonitis associated with GVH. We will examine the role of virus replication in the genesis of pneumonitis and determine the lung structures which support MCMV replication using in situ hybridization methods. We will also examine the quatitative relationship of MCMV lung replication to GVH and interstitial pneumonitis by modulating virus replication in the lungs, using antiviral agents, vaccination, and Ts MCMV mutants. We will also determine if MCMV is present during pneumonitis in which virus cannot be recovered by culture of lung homogenates. The host immune processes operating in the lung during GVH/MCMV interstitial pneumonitis will also be examined. We will characterize the cellular changes which occur in the lungs, determining the lymphocyte phenotypes and the origin (donor/recipient) of the cells present in the lung. We will also examine the functional CMI processes operating in the lung, and determine if these are directed at MCMV or host H2 determinants. By immunohistochemical methods, we will examine the alterations in expression of H2 antigens in the lungs during pneumonitis. We will also determine if modification of the host immune responses will alter interstitial pneumonitis. Finally, we will determine if GVH to minor HA will alter MCMV replication in the lung or lead to interstitial pneumonitis. These studies should substantially increase our understanding of the pathogenesis of CMV pneumonitis and the interactions of viral and host factors which may be involved in the genesis of disease.