Programming, demarcating, and manipulating CD8+ T-cell memory

In response to infection, antigen-specific CD8+ T cells undergo massive expansion in numbers, acquire effector mechanisms, and disseminate throughout the body. The expansion phase is followed by a contraction (death) phase, where 90-95% of antigen-specific CD8+ T cells are eliminated. The remaining antigen-specific CD8+ T cells form the initial memory pool, which can be stably maintained for life. In this review, we discuss evidence that early events after infection 'program' CD8+ T cells to expand, contract, and generate memory in a fashion that is largely insensitive to the duration of infection or antigen display. Recent data demonstrate, despite numerical stability, that memory CD8+ T-cell populations undergo phenotypic and functional changes with time after immunization. However, the early suggestion that specific markers can be used to identify memory CD8+ T cells has not been supported by recent studies. Thus, we argue that specific functional characteristics, such as the ability to persist and undergo vigorous secondary expansion leading to elevated memory cell numbers, remain the best markers of 'good' memory cells. Finally, we discuss experimental approaches to manipulate and accelerate generation of CD8+ T cells with memory characteristics, and how these systems can inform both basic and applied immunology.