Compared with adults, the circulating Vγ2Vδ2 T-cell population in cord blood is present at low levels and does not show the strong bias for Vγ2-Jγ1.2 rearrangements. These features may be a result of limited exposure to stimulatory phosphoantigens, lack of T-cell-derived interleukin-2 (IL-2) or both. In cord blood mononuclear cell cultures, a single round of stimulation, using aminobisphosphonates to elevate phosphoantigen levels, resulted in expansion of adult-like Vγ2 chains and accumulation of memory cells with cytotoxic potential. Selection was similar using IL-2 or myeloid-derived IL-15. The Vγ2Vδ2 T cells present in neonates are capable of generating potent immune responses even when relying on IL-15.