CYTOMEGALOVIRUS PNEUMONITIS: THE ROLE OF TNF A AND B

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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.