The mechanisms of CD4+ T-cell memory formation in the immune system are debated. With the well-established concept of memory formation in the central nervous system (CNS), we propose that formation of CD4+ T-cell memory depends on the interaction of two different cell systems handling two types of stored information. First, information about antigen (event) and challenge (context) is taken up by antigen-presenting cells, as initial storage. Second, event and context information is transferred to CD4+ T cells. During activation, two categories of CD4+ T cell develop: effector CD4+ T cells, carrying event and context information, enabling them to efficiently focus their response to tissues under attack; and persisting CD4+ T cells, providing context-independent antigen-specific memories and long-term storage. This novel hypothesis is supported by the observation that mammalian sleep can improve both CNS and CD4+ T-cell memory.