The overall aim of this proposal will be to determine the role of individual phenotypically and functionally defined T lymphocte subpopulations in the control of three distinct stages of the host-virus relationship following infection with herpes simplex virus (HSV). The stages to be studied will be (i) the clearance of virus from the primary site of infection, (ii) the establishment of latent infection in neurons of local sensory ganglia, and (iii) the reactivation of virus from the latent state. The first objective will be to determine the rate of appearance and frequency of precursors of immunologically functional HSV-specific helper and cytotoxic T lymphocytes in local lymphoid tissue following a local infection with HSV, and to extend the study to immunized mice responding to a secondary infection. This will be assessed in two strains of inbred mice which exhibit different levels of innate resistance to HSV infection. C57BL/6 (H-2b) mice are relatively resistant to infection with HSV, while BALB/c (H-2d) mice are moderately sensitive. Innate resistance is genetically determined, and has been shown to have an immunological basis in the T lymphocyte-mediated component of the immune response. This suggests that the sensitive strains may have a fundamental immunological deficiency that precludes the successful initial control of HSV multiplication and dissemmination. By comparing the early T lymphocyte repsonse in these two strains, it will be possible to determine whether an underlying T lymphocyte-mediated response is responsible for this observation. The second objective will be to determine the role of the T lymphocyte response in the control of HSV multiplication and clearance from the primary site of infection, the establishment of latency and subsequent reactivation of HSV from the latent state. This will be studied by the adoptive transfer of phenotypically and functionally defined HSV-specific T lymphocyte subsets to naive recipients, and by selective in vivo depletion of these subsets by treatment with monoclonal antibodies specific for differentiation isoantigens associated with each funcitonal subset. The third objective will be to determine the role of HSV viral glycoproteins involved, and the mode in which these components are presented to the HSV-specific T lymphocytes that results in an effective response.
