This proposal is designed to investigate the role of T lymphocytes in the process of recovery from experimental Respiratory Syncytial Virus (RSV) infection and in the induction of pulmonary injury during the host response to RSV infection. The proposed studies are an outgrowth of our long-standing interest in T lymphocyte function in viral infection. Our experimental approach will be to isolate and characterize clonal populations of murine CD8+ T lymphocytes and CD4+ Th1 and Th2 T lymphocytes directed to the RSV F and/or G glycoproteins. This characterization will include analysis of the production of effector lymphokines including IFN-gamma, IL-4 and IL-5 and determination of T lymphocyte mediated cytolytic activity. These defined clones will then be adoptively transferred into syngeneic RSV infected recipients in order to ascertain the effect of these defined T lymphocyte populations on pulmonary virus clearance and pulmonary injury. Related to experiments will employ RSV infected mice rendered genetically deficient in the production of specific lymphokines by homologous recombination in order to precisely evaluate the role of these T lymphocyte products in virus clearance and in the immunopotentiation of pulmonary injury during RSV infection. Based on these in vitro and in vivo studies, strategies for experimental vaccination will be developed to selectively prime memory T cells with optimal anti viral activity but minimal capacity for immunopotentiation of pulmonary injury. The experiments outlined in this proposal will provide new information on the function and mechanism of action of T lymphocytes in Respiratory Syncytial Virus infection and in RSV associated pulmonary injury. This information should be of immediate value in the design of effective RSV vaccines and will yield basic information on the nature of the interaction between viruses and the immune system.
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