Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is a type 2 transmembrane protein belonging to the TNF family, which preferentially induces apoptotic cell death in a wide variety of tumor cells but not in most normal cells. 1, 2 We recently reported that a subpopulation of natural killer (NK) cells in adult mouse liver constitutively expressed TRAIL in an interferon γ (IFN-γ)–dependent manner. 3 These liver NK cells were partially responsible for the natural antimetastatic function against TRAIL-sensitive tumor cells. 3, 4 We have also demonstrated that IFN-γ–mediated TRAIL induction on NK cells plays a substantial role in the IFN-γ–dependent antimetastatic effects of IL-12 and α-galactosylceramide (α-GalCer). 5 Given that both NK cells and IFN-γ have been implicated in natural protection against primary tumor development, 6, 7 TRAIL may be in part responsible for the NK cell-mediated and IFN-γ–dependent mechanisms of tumor surveillance in the adult. 8, 9

Despite a recent expansion in our knowledge concerning NK cell receptors, 10, 11 the in vivo development of mouse NK cell effector function is still poorly defined. It has been suggested that a CD122+ NK1. 1JDX5J population contains the early NK cell-committed precursor, 12 but subsequent developmental stages, including the acquisition of cytotoxic molecules and cytokine-producing function, are not well understood. 13 The presence of a high frequency of phenotypically immature NK cells in the mouse liver was shown in a recent report. 14 In