Successful antiviral vaccination strategies rely on the induction of virus-specific memory cells. Upon reexposure to the virus, these memory cells are responsible for generating protective secondary immune responses. Despite its basic and clinical importance, the fundamental mechanisms responsible for the generation of protective immunity are poorly understood. We are investigating the mechanisms of protective antiviral T cell responses using lymphocytic choriomeningitis virus (LCMV) infection of mice as a model system. In this system protective immunity manifests as cytotoxic T lymphocyte (CTL)-mediated resistance to lethal choriomeningitis following intracranial (i.c.) infection with LCMV. We have found that, in contrast to normal animals, mice that are deficient in the chemotactic cytokine macrophage inflammatory protein (MIP)-1alpha do not develop protective immunity against i.c. infection with LCMV. These results indicate, therefore, that MIP-1alpha is crucial for the development of protective antiviral immunity. The experiments proposed in this application are designed to determine the mechanisms by which MIP-1alpha promotes T cell-mediated protective antiviral immune responses. This information should provide a framework for the ration design of vaccines that elicit protective immunity against virus infections.
The specific aims of this proposal are threefold. 1. To determine if LCMV-specific memory T cells are maintained in the absence of MIP-1alpha. 2. Elucidate the importance of MIP-1alpha in trafficking of virus- specific CD8+ cells. 3. To identify the molecular interactions required for MIP-1alpha- dependent protective antiviral immunity.
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| Low, Q E; Drugea, I A; Duffner, L A et al. (2001) Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice. Am J Pathol 159:457-63 |
