CYTOMEGALOVIRUS PNEUMONITIS DURING GRAFT VS HOST DISEASE

虽然巨细胞病毒（CMV）引起的间质性肺炎是一种 免疫功能低下患者发病率的重要来源， 已知CMV间质性肺炎的发病机制， 病毒和宿主因素对这一起源的相对贡献 过程 我们以前观察到，小鼠巨细胞病毒（MCMV）感染显着 增强对主要组织相容性抗原（HA）的GVH反应， 至严重间质性肺炎，单独使用病毒或GVH时未观察到。 初步数据表明，MCMV/GVH合并患者的肺炎是 而不是由于GVH引起的肺中病毒复制增加的结果。 本提案的目的是确定病毒和宿主免疫力 MCMV间质性肺炎发病中的重要因素 与GVH有关。 我们将研究病毒复制在 肺炎的发生，并确定支持MCMV的肺结构 使用原位杂交方法复制。 我们亦会研究 MCMV肺复制与GVH和间质性的定量关系 通过调节病毒在肺部的复制，使用抗病毒药物 试剂、疫苗接种和Ts MCMV突变体。 我们还将确定MCMV是否 在病毒不能通过培养回收的肺炎期间存在 肺匀浆。 在GVH/MCMV期间在肺中运行的宿主免疫过程 还将检查间质性肺炎。 我们将描述 发生在肺部的细胞变化，决定淋巴细胞 表型和存在于细胞中的细胞的来源（供体/受体） 肺。 我们还将研究在 肺，并确定这些是否针对MCMV或宿主H2决定簇。 通过免疫组织化学方法，我们将检查 肺炎时肺内H2抗原的表达。 我们还将 确定宿主免疫反应的改变是否会改变 间质性肺炎 最后，我们将确定GVH到轻微HA是否会改变MCMV的复制 或导致间质性肺炎。 这些研究应 大大增加了我们对CMV发病机制的了解 肺炎和病毒和宿主因素的相互作用， 参与疾病的发生。

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.