Defective IL-15 signaling contributes to NK defect. (A-B) Tumor growth reduces IL-15Rα^hi cells in the bone marrow. Bone marrow cells were isolated from the control PBS-treated or tumor-bearing mice at 3 weeks after tumor-cell challenge and stained with either anti-IL-15Rα antibody or isotype control. (A) Representative profile IL-15Rα expression. The number in the panels shows the percentage of cells in the IL-15Rα^hi-cell gate. (B) Summary data on the percentage of IL-15Rα^hi cells. A significant difference was observed between tumor-bearing and control mice. (C-D) Transgenic overexpression of IL-15 over-comes NK-cell differentiation defect. IL-15Tg and wild-type littermate controls were injected with EL4 or PBS. Four weeks later, the mice were killed, and bone marrow NK cells were analyzed for CD11b expression. Data shown in panel C are representative FACS profiles of gated NK1.1⁺CD3^- NK cells of 3 independent experiments, whereas those in panel D are means and SEM of the percentage of reduction of CD11b^hi cells in tumor-bearing mice. Student t test reveals significant difference in the percentage of CD11b^hi cells in non-transgenic littermates.