Our lab is interested in understanding how T cells respond to chronic antigen stimulation during persistent viral infections, particularly cytomegalovirus (CMV) infections. CMV is a ubiquitous herpesvirus that infects most people world-wide and persists for life. In immunocompromised individuals, CMV can be a major pathogen, causing severe morbidity and death. In healthy individuals, CMV is continuously controlled by the immune system and causes little or no pathology, thanks largely to a potent T cell response. The constant immune surveillance of CMV-infected cells results in a slow accumulation of virus-specific CD8+ T cells in healthy people such that on average, CMV-specific T cells comprise 4% to 5% of all T cells in circulation. However, the mechanisms by which these T cells are generated and maintained are not understood. This is important for two reasons. First, CMV-specific T cells isolated from healthy donors are being used experimentally to control CMV infection in immune compromised patients. Second, CMV has been proposed as a vaccine vector to stimulate large T cell populations specific for recombinant antigens encoded in the CMV genome. In both cases, a better understanding of how these populations develop and persist as well as how they respond to new antigen encounters will improve these therapeutic approaches. To study the immune response to CMV, we use murine cytomegalovirus (MCMV), a homologue of human CMV (HCMV) and a natural mouse pathogen. Like HCMV, infection of mice with MCMV results in the slow accumulation of functional, virus-specific T cells over time. Currently we focus on two broad areas of research: 1) the homeostasis of MCMV-specific T cells that enables their maintenance over time and 2) the response of MCMV-specific T cells to re-stimulation in the context of adoptive immunotherapy.