Figure 6. Exogenous IL-2 supports CIML NK cells in a NSG xenograft model.

(A) Purified human NK cells were pre-activated with IL-12, IL-15, and IL-18 (CIML) or low dose IL-15 only (control) for 16 hours, washed, and identical numbers of NK cells were transferred into NSG mice, followed by injections of 75,000 IU i.p. of rhIL-2 every other day. After 7 days, mice were assessed for human NK cell content, and CIML NK cell recall responses. (B) Representative flow plots from the peripheral blood of mice injected with the same number of CIML or control NK cells from the same donor 7 days earlier. Human CD45⁺ cells are CD56⁺CD3⁻ NK cells with preserved CD56^bright and CD56^dim NK cells subsets. (C) Summary data from 3 different NK cell donors transferred into a total of 12 NSG mice demonstrating superior engraftment of CIML, compared to control, NK cells. The ratio of human: mouse CD45+ cells, representing the relative abundance of human NK cells, is used to control for differences in blood volume obtained. (D) Mouse splenocytes containing adoptively transferred human NK cells were evaluated for a recall IFN-γ response following IL-12+IL-15 restimulation, demonstrating that CIML NK cells exhibit preserved, enhanced functionality in this xenograft model. Significance was assessed by T test, with *P<0.05, **P<0.01, and ***P<0.001.