Expression of one or more natural killer (NK) receptors on T cells may correlate with effector function. This study investigated the frequency of neonatal NK receptor-positive (NKR+) T cells and their expansionary properties with interleukin-2 (IL-2), IL-7, or IL-15. While cord blood contains significantly decreased frequencies of NKR+ T cells compared with adult blood, newborn CD56+CD3+ cells could be expanded 200-fold during culture with IL-15. By depleting CD56+ cells, we were able to determine that this expansion was due to a subpopulation of T cells acquiring CD56 expression. Moreover, CD56 acquisition was associated with a distinct CD8+CD25+ interferon gamma-positive (IFN-gamma+) phenotype. This property could therefore be exploited during bone marrow reconstitution and may partially account for the resilience of the newborn to infection.