IL-15 primes NK cells with improved survival and cytolytic activity following cytokine withdrawal. Primary human NK cells were isolated from fresh peripheral blood mononuclear cells (PBMCs) and activated with IL-2 or IL-15 (both at 18.3 ng/mL) for 48 hours. (A) Cytolytic capacity against NK-sensitive target K562 (effector-to-target [E:T] ratio = 5:1) and proliferation of resting or cytokine activated human NK cells were measured by chromium release assay and thymidine incorporation assay, respectively. Following cytokine activation for 48 hours, NK cells were cultivated without cytokines (cytokine withdrawal) for an additional 24 hours and tested for their (B) cytolytic activity against K562 cells or (C) viability. Flow cytometry analysis of NK cells following cytokine activation including (D) frequencies of CD25⁺ cells, (E) expression of membrane-bound cytokines, and cytokine receptor complexes; intracellular expression of Bcl-2; and phosphorylation of STAT-3 (Y705) and STAT-5 (Y694). Results from multiple donors (n > 5) were summarized and are presented as mean ± SD. *P < .05; ***P < .001; Mann-Whitney nonparametric U test. cyt., cytokine; n.s., not significant.