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 感染可累及多个宿主组织，肺部经常 与致命性巨细胞病毒感染有关。在这些实验中，几只小鼠 将利用CMV感染的模型来探索细胞因子， 肿瘤坏死因子-a和淋巴毒素(TNF-b)作为组织损伤的介质。的作用 亚致死和致死病毒后急性巨细胞病毒感染中的肿瘤坏死因子-a和肿瘤坏死因子-b 我们将对挑战进行审查。使用急性巨细胞病毒感染的模型， 致死性和亚致死性病毒在组织中表达的肿瘤坏死因子数量 比较外源性肿瘤坏死因子对急性巨细胞病毒感染的影响 将对感染情况进行监测。抗体被动转移的效果 将确定肿瘤坏死因子对病毒复制的影响。探索肿瘤坏死因子的作用 在肺损伤中，肺孢子虫相关的MCMV和 将使用移植物抗宿主病，比较在 巨细胞病毒肺部感染和肺孢子虫。肺细胞产生肿瘤坏死因子 将对肺孢子虫进行检查，并将确定是否 产生是抗原特异性的或MHC受限的。被动的影响 抗肿瘤坏死因子抗体和淋巴毒素在巨细胞病毒肺孢子虫上的转移也将 要下定决心。该项目的具体目标是：确定 肿瘤坏死因子-α和淋巴毒素在急性巨细胞病毒感染中的作用 肿瘤坏死因子-α和淋巴毒素在肺孢子虫病发病机制中的作用 与巨细胞病毒联合感染和生殖器疱疹相关。

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.