Zoledronate and IL-2 promote cellular responses in the CD56⁺ subset in a synergistic, time- and dose-dependent fashion. (A) CD56⁺ cells (10⁶/mL) were either left untreated or stimulated with IL-2, zoledronate, or zoledronate plus IL-2 in round-bottomed 96-well plates. Microscopic monitoring of cell cultures from day 3 to day 5 showed cell aggregation as an indicator of cell activation. (B) CD56⁺ cells (10⁶/mL) were stimulated with IL-2 at 100 U/mL and increasing concentrations of zoledronate. IFN-γ levels determined in culture supernatants on day 5 increased in a dose-dependent fashion (mean values of duplicate cultures). (C) CD56⁺ cells (1.5 × 10⁶/mL) were stimulated for 72 hours with either IL-2 alone (100 U/mL) or with zoledronate (2 μM) plus IL-2. Staining of surface Vδ2 and intracellular IFN-γ showed that Vδ2⁺ cells produced IFN-γ in response to zoledronate plus IL-2 but not in response to IL-2 alone.