IL-21 suppresses IL-2–induced effector CD8⁺ T-cell differentiation and substantially prevents IL-2–mediated impairment of CD8⁺ T cells for adoptive transfer. Naive pmel-1 CD8⁺ T cells were antigen-primed with 10 ng/mL IL-2, IL-21, or 10 ng/mL IL-2 combined with 10 ng/mL IL-21. (A) Eomes expression was determined by RT-PCR 3 days following priming. (B) Granzyme B expression was assessed by flow cytometry 3 days after priming. The mean fluorescence intensity is indicated. (C) Pmel-1 CD8⁺ T cells were primed with cognate antigen and 10 ng/mL of the indicated cytokine(s). After 4 days, 5 × 10⁵ cells per mouse were adoptively transferred into tumor-bearing recipients. Vaccine and IL-2 were administered to all but the “No treatment” group. Tumor responses were assessed with serial measurements. Error bars represent the standard error of the mean.