In vivo antitumor effect of IL-21 is NK- and T-cell dependent. In (A-B), C57BL/6 mice (n = 5 per group) depleted of NK or treated with irrelevant Ig (A), CD4⁺ T and/or NK cells (B), and CD8⁺ T and/or NK cells (C) were SC inoculated with FC-muMCL1 cells. Depicted are Kaplan–Meier survival curves of mice treated with IL-21 or PBS (control) as described in “Materials and methods.” (D-E) FC-muMCL1 cells or (F) normal human B cells from PBL were labeled with ⁵¹Cr and incubated with purified mice NK cells (D), or mice CD4⁺ T cells (E), or human CD4⁺ T cells (F) at the indicated T:E ratios. Percentage of specific lysis was measured based on the ⁵¹Cr release. All samples were run in triplicates (n = 3). Data in panels A-E are representative of 2 independent experiments. Error bars represent standard error of the mean. **P < .01; ***P < .0005.