IL-2 and IL-21 mediate opposing effects on antigen-induced CD8⁺ T-cell differentiation. Priming naive CD8⁺ T cells with IL-2 or IL-15 promotes their cytolytic effector function but impairs their antitumor capability in vivo. In contrast, priming naive CD8⁺ T cells with IL-21 suppresses their cytolytic effector function but enhances their ability to mediate tumor regression in vivo.