In the unimmunized animal, there is a race between the proliferation of the invading pathogen versus the proliferation of the responding lymphoid cells that will decide the fate of the host. For a number of pathogenesis the odds are not good and the outcome can be death. If the host survives, a memory population is now established and the odds for survival can be very different upon reexposure. Immunization has provided us with the means to protect us from many previously deadly diseases. However, many disease organisms against a number of important pathogens and new antibiotic resistant mutants pose a major problem. For these reasons, efforts to develop more efficient immunization procedures are vital. It is thus somewhat paradoxical that we know relatively little about the mechanisms that control the development and maintenance of immune memory. In this project, we will study the regulation of CD8 T cell memory. We have developed a quantitative model system for memory studies in which naive CD8 T cells from T cell receptor transgenic mice are stimulate for four days in vitro and the resulting effectors give rise to memory cells upon adoptive transfer into synergistic hosts. We will use this quantitative model to study the parameters of CD8 T cell memory generation, persistence and function.
In Aim 1, we will identify the nature of the memory precursor cell and the parameters that control the generation of memory cell populations in vitro.
In AIM 2, we will identify the factors that regulate memory T cell populations in the host.
In AIM 3, we will study the nature and function of diverse CD8 memory T cell populations. We will collaborate with Dr. Swain (Project 1) to investigate differences in the control of CD4 and CD8 T cell memory that we have uncovered and will collaborate with Dr. Bradley (Project 3) to investigate regional differences in the migration and behavior of CD4 and CD8 memory cells. We anticipate that the results of our studies will lead to a better understanding of immunological memory and improved strategies in vaccine development and immunization protocols, which are needed to combat traditional and emerging pathogens.
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