We are developing transgenic animals where antigen presentation by dendritic cells can be experimentally controlled in vivo. For CD4+ T cells we have previously found that antigen has to be presented throughout the expansion phase for effector and memory cell differentiation. For CD8+ T cells it has been reported that a short antigen pulse is sufficient for programming the complete response. We are currently characterizing a regulatable system for CD8+ T cells to compare the two T cell subsets in their requirements for antigen persistence and hope to learn more about the regulation of the cell cycle in T lymphocytes. It is likely that a deeper understanding of these issues will help us to make better vaccines and to interfere more specifically with autoimmune disease.