Shaping and reshaping CD8 + T-cell memory

Key Points Shortly after infection and/or vaccination, rare, antigen-specific CD8 + T cells encounter mature antigen-expressing dendritic cells (DCs), become activated and undergo extensive expansion in numbers following a 'programme' that is largely independent of the duration of the infection and/or functional antigen that is displayed. Most of the primary effector CD8 + T cells die during a programmed contraction phase and the surviving CD8 + T cells initiate the heterogeneous memory pool that slowly undergoes additional phenotypic and functional changes with time. Proliferative expansion, phenotype, and function of CD8 + T-cell responses to infection are altered when the number of T-cell receptor (TCR)-transgenic CD8 + T cells transferred is sufficiently high to prevent the endogenous CD8 + T-cell response to the same epitope. The specific number of TCR-transgenic T cells that can be used to mimic the endogenous response may be influenced by the affinity of the TCR, the number of endogenous precursors and the pathogen or vaccination method used, and must be empirically determined for each experimental model. The requirements for memory CD8 + T-cell maintenance and the functional characteristics of the CD8 + T-cell memory populations are dramatically different following persistent infection (that is, when antigen and pathogens are not cleared from the host) compared with acute infection. Pro-inflammatory cytokines, for example type I interferons (IFNs), IFNγ or interleukin-12, can act directly on responding CD8 + T cells during the expansion and contraction phases of CD8 + T-cell response to infection to affect crucial aspects of memory CD8 + T-cell generation. The early inflammatory milieu dictates the rate at which CD8 + T cells acquire phenotypic and functional characteristics of memory suggesting that the process of memory CD8 + T-cell generation that depends on the nature of the pathogen or vaccination strategy used to elicit the response and that select aspects of memory CD8 + T-cell generation may be manipulable. The characteristics of secondary memory CD8 + T cells are quite different than the primary CD8 + T-cell populations. They undergo protracted contraction, exhibit substantially delayed upregulation of central memory CD8 + T-cell characteristics, show decreased memory turnover (compared with primary memory CD8 + T cells) and exhibit (on per cell basis) enhanced protection against pathogen re-encounter. Here, John Harty and Vladimir Badovin