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The Journal of Immunology, 2004, 173: 900-909.
Copyright © 2004 by The American Association of Immunologists

IL-21 Enhances and Sustains CD8+ T Cell Responses to Achieve Durable Tumor Immunity: Comparative Evaluation of IL-2, IL-15, and IL-211

Adrianna Moroz*, Cheryl Eppolito*, Qingsheng Li*, Jianming Tao*, Christopher H. Clegg{dagger} and Protul A. Shrikant2,*

* Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263; and {dagger} Department of Immunology, Zymogenetics, Seattle, WA 98102

Cytokines that use the common receptor {gamma}-chain for regulating CD8+ T cell responses to Ag include IL-2, IL-15, and the recently identified IL-21. The ability of these cytokines to regulate antitumor activity in mice has generated considerable interest in understanding their mode of action. In this study we compare the abilities of IL-2, IL-15, and IL-21 to stimulate immunity against tumors in a syngeneic thymoma model. Durable cures were only achieved in IL-21-treated mice. By monitoring both endogenous and adoptively transferred tumor Ag-specific CD8+ T cells, it was determined that IL-21 activities overlap with those of IL-2 and IL-15. Similar to IL-2, IL-21 enhanced Ag activation and clonal expansion. However, unlike IL-2 treatment, which induces activation-induced cell death, IL-21 sustained CD8+ T cell numbers long term as a result of increased survival, an effect often attributed to IL-15. These findings indicate that the mechanisms used by IL-21 to promote CD8+ T cell responses offer unique opportunities for its use in malignant diseases and infections.


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