IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro

Recent studies in mice have shown that although interleukin 15 (IL-15) plays an important role in regulating homeostasis of memory CD8(+) T cells, it has no apparent function in controlling homeostatic proliferation of naive T cells. We here assessed the influence of IL-15 on antigen-independent expansion and differentiation of human CD8+ T cells. Both naive and primed human T cells divided in response to IL-15. In this process, naive CD8(+) T cells successively down-regulated CD45RA and CD28 but maintained CD27 expression. Concomitant with these phenotypic changes, naive cells acquired the ability to produce interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), expressed perforin and granzyme B, and acquired cytotoxic properties. Primed CD8(+) T cells, from both noncytotoxic (CD45RA(-)CD27(+)) and cytotoxic (CD45RA(+)CD27(-)) subsets, responded to IL-15 and yielded ample numbers of cytokine-secreting and cytotoxic effector cells. In summary, all human CD8(+) T-cell subsets had the ability to respond to IL-15, which suggests a generic influence of this cytokine on CD8(+) T-cell homeostasis in man. (C) 2003 by The American Society of Hematology.