IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells
1 Department of Melanoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
2 Present address: U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 1401 Rockville Pike, HFM-675, Rockville, MD 20852, USA
Correspondence to: P. Hwu; E-mail: phwu{at}mdanderson.org
IL-21, a recently identified member of the common 
-chain (c) receptor cytokine family, has been shown to be an important regulator of both innate and adaptive immune responses. In this study, we investigated whether IL-21 could synergize with another c cytokine, IL-7, to induce enhanced proliferation and effector function of tumor antigen-specific CD8+ T cells. Our results showed that IL-21 could significantly augment the IL-7-induced expansion of cytotoxic T cells, possibly by preventing the cytokine-induced down-regulation of the IL-7R
(CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of Th1 and inflammatory cytokines by activated T cells, including IFN-, IL-2, tumor necrosis factor-, granulocyte macrophage colony-stimulating factor, IL-1ß and IL-6. Finally, the addition of IL-21 to IL-7-cultured CTLs resulted in a considerably higher level of cytolytic activity, as measured by specific killing of tumor cells or antigen-pulsed target cells. These results suggest that IL-21 may play a cooperative role with IL-7 in modulating primary CD8+ T-cell responses and may have important implications for immunotherapy of cancer.
Keywords: cytotoxic T cell, IL-21, IL-7, immunotherapy, tumor immunology
* These authors contributed equally to this study.
Received 22 February 2007, accepted 19 July 2007.