The generation of memory T cells in immune responses has been extensively studied over recent years, yet the requirements for production and persistence of a functional memory pool are still unclear. For example, while there is compelling evidence that survival of memory cells does not require TCR–MHC engagements (1, 2), recent evidence indicates that such interactions may be needed to maintain functional activity of these cells (3, 4). Furthermore, there is growing evidence that cytokines play a major role in deciding the fate of CD8 memory cells, although the precise mechanisms by which these effects are mediated remain unknown.

Several new reports, one in the Journal of Immunology (5) and four (6–9) in this issue, now provide further insight into the key cytokine players which induce and maintain the CD8 T cell memory pool. In support of previous studies, IL-15 is implicated as a key regulator of CD8 memory T cell homeostasis. Interestingly, the current data show that in at least one case (5), IL-15 deficiency diminishes the magnitude of CD8 T cell expansion in the primary response, resulting in the production of fewer memory cells. Moreover, the results reveal that once memory cells are generated, IL-15 is critical for their basal proliferation. Surprisingly, several of these studies indicate that, in the absence of IL-15, CD8 homeostasis in immunodeficient hosts can also be maintained by IL-7 as long as the latter is not made limiting by competition with other cells. These data lead to a model where cytokine competition between T cell subsets can influence the fate of the memory pool (Fig. 1). A specialized role for IL-15 in the regulation of T cell memory was suggested by the ability of IL-15 (or IL-15–inducing stimuli) to stimulate proliferation of memory CD8 T cells but not memory CD4 T cells or naive T cells in vivo (10). Furthermore, overexpression of IL-15 leads to persistence of increased numbers of antigen-specific CD8 memory cells after Listeria infection (11). These findings were amplified by analysis of IL-15 and IL-15R knockout mice which display reduced numbers of CD8 T cells in the