Proliferation of memory-phenotype (CD44(hi)) CD8(+) cells induced by i
nfectious agents can be mimicked by injection of type I interferon (IF
N 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 b
e TCR independent. Since IFN I inhibits proliferation in vitro, IFN I-
induced proliferation of CD8(+) cells in vivo presumably occurs indire
ctly through production of secondary cytokines, e.g., interleukin-2 (I
L-2) or IL-15. We show here that, unlike IL-2, IL-15 closely mimics th
e effects of IFN I in causing strong and selective stimulation of memo
ry-phenotype CD44(hi) CD8(+) (but not CD4(+)) cells in vivo; similar s
pecificity applies to purified T cells in vitro and correlates with mu
ch higher expression of IL-2R beta on CD8(+) cells than on CD4(+) cell
s.