CYTOMEGALOVIRUS PNEUMONITIS: THE ROLE OF TNF A AND B

描述：（改编自申请人的摘要。）虽然严重的CMV 感染可以涉及许多宿主组织，肺经常被感染。 与致命的巨细胞病毒感染有关 在这些实验中， 将利用CMV感染的模型来研究细胞因子， 肿瘤坏死因子-a和光毒素（TNF-b），作为组织损伤的介质。 的作用 巨细胞病毒亚致死和致死性感染后TNF-α和B的变化 挑战将被审查。 使用急性CMV感染模型， 在致死和亚致死病毒期间组织中表达的TNF量 将比较激发和外源性TNF对急性CMV的影响， 将监测感染情况。 抗体被动转移的影响 将确定TNF对病毒复制的影响。 探讨肿瘤坏死因子（TNF）的作用 在肺损伤中，肺孢子虫相关MCMV小鼠模型和 将使用移植物抗宿主病， MCMV肺部感染和肺孢子虫。 肺细胞产生TNF 在肺孢子虫期间将进行检查，并将确定是否 生产是抗原特异性的或MHC限制性的。 被动的影响 MCMV肺孢子虫上的TNF和α-光毒素抗体转移也将 下定决心。 该项目的具体目标是： TNF-α和巨噬细胞毒素在急性MCMV感染中的作用; 肿瘤坏死因子-α和肺光敏素在肺孢子虫发病中的作用 与MCMV感染和GVH疾病联合相关。

DESCRIPTION: (Adapted from the applicant's abstract.) While serious CMV infections can involve a number of host tissues, the lungs are frequently involved in lethal CMV infections. In these experiments several murine models of CMV infection will be utilized in order to explore the cytokines, TNF-a and lymphotoxin (TNF-b), as mediators of tissue damage. The role of TNF-a and b in acute MCMV infection following sublethal and lethal virus challenge will be examined. Using a model of acute CMV infection, the amount of TNF expressed in tissue during lethal and sublethal virus challenge will be compared and the effect of exogenous TNF on acute CMV infection will be monitored. The effects of passive transfer of antibody to TNF on virus replication will be determined. To explore the role of TNF in lung injury, a murine model of pneumocystis associated MCMV and graft-versus-host disease will be used, comparing the levels of TNF during MCMV lung infection and pneumocystis. The production of TNF by lung cells during pneumocystis will be examined and it will be determined if production is antigen-specific or MHC-restricted. The effects of passive transfer of antibody to TNF and lymphotoxin on MCMV pneumocystis will also be determined. The Specific Aims of this project are: to determine the role of TNF-a and lymphotoxin in acute MCMV infection; and to determine the role of TNF-a and lymphotoxin in the pathogenesis of pneumocystis associated with combined MCMV infection and GVH disease.