Cytokines play a central role in regulating the homeostasis of naıve and memory T cells and their responses to pathogens. Surprisingly, not much is known about the ability of exogenously administered cytokines to affect the formation of memory T cells. In a recent study, Nanjappa et al. 1 have shown that infusion of interleukin (IL)-7 during the contraction phase of a T-cell response can augment the accumulation of functional viral-specific memory T cells. As the formation of a large pool of memory T cells is the main goal of vaccination, these findings suggest that cytokines could be applied therapeutically to enhance vaccine efficacy. Clues to the potential utility of IL-7 and related cytokines as adjuvants can be gleaned by their roles in T-cell homeostasis. IL-7 is a member of a family of cytokines that all share the common gamma chain (γc) in their receptor but also have a unique ligand-binding α chain. Although many of the γc cytokines have an antiapoptotic effect on T cells in vitro, only IL-2, IL-7 and IL-15 appear to influence T-cell homeostasis in vivo. 2 Early T-cell precursors in the thymus, as well as naıve and memory T cells in the periphery depend on IL-7 for their survival, thus, making this cytokine the major regulator of T-cell homeostasis. 3 A low level of IL-7 is thought to be produced constitutively by stromal cells in lymphoid organs to keep a finite number of naıve and memory T cells alive. In addition to IL-7, memory CD4 and CD8 T cells are dependent on signals from IL-15 for their survival and turnover. 2 IL-7 receptor (CD127) levels are low on regulatory T cells, which are responsible for maintaining peripheral immune tolerance; these cells appear to be the only cells in nonimmunized mice that express the high-affinity IL-2 receptor and are almost exclusively dependent on IL-2 for their survival. 4 Therefore, the maintenance of a peripheral T-cell pool with a normal composition of resting naıve and memory T cells is supported by IL-2, IL-7 and IL-15.

Although the mechanisms that control the formation of memory T cells are not known, the powerful ability of IL-2, IL-7 and IL-15 to regulate T-cell homeostasis suggests that they could influence this process. Memory T cells are generated from a small fraction (5–10%) of the effector T cells after clearance of the pathogen (see Figure 1). The role of cytokines in memory T-cell formation was largely unexplored until the recent finding that effector CD8 T cells destined to differentiate into memory T cells expressed CD127. 5 Although this finding suggested that IL-7 provides the key survival signal during effector-to-memory transition, subsequent work showed that CD127 expression per se was not sufficient to ensure survival and continued differentiation of effector CD8 T cells. 6, 7 The lack of such a strict correlation indicated that additional factors are involved in regulating the effector-to-memory transition. The identity of