Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15

Proliferation of memory-phenotype (CD44(hi)) CD8(+) cells induced by infectious agents can be mimicked by injection of type I interferon (IFN I) and by IFN I-inducing agents such as lipopolysaccharide and Poly I:C; such proliferation does not affect naive T cells and appears to be TCR independent. Since IFN I inhibits proliferation in vitro, IFN I-induced proliferation of CD8(+) cells in vivo presumably occurs indirectly through production of secondary cytokines, e.g., interleukin-2 (IL-2) or IL-15. We show here that, unlike IL-2, IL-15 closely mimics the effects of IFN I in causing strong and selective stimulation of memory-phenotype CD44(hi) CD8(+) (but not CD4(+)) cells in vivo; similar specificity applies to purified T cells in vitro and correlates with much higher expression of IL-2R beta on CD8(+) cells than on CD4(+) cells.