The generation of strong and specific CD8 T cell responses is important in the control of viral infections. Costimulatory molecules provide signals necessary for the development or maintenance of these responses. A major focus of our laboratory is to investigate the role of costimulatory molecules of the TNFR and CD28 families in antiviral responses. Our aim is to translate information obtained using murine models to the study of these molecules using human cells. We have devised an in vitro system using recombinant replication- deficient adenovirus to deliver costimulatory molecules to antigen-presenting cells that are then used to stimulate autologous T cells from both healthy and HIV-infected individuals. Here we describe our findings and discuss the implications of incorporating costimulatory molecules into viral vector vaccine strategies.