TY - JOUR
T1 - IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells
AU - Liu, Shujuan
AU - Lizée, Gregory
AU - Lou, Yanyan
AU - Liu, Chengwen
AU - Overwijk, Willem W.
AU - Wang, Gang
AU - Hwu, Patrick
PY - 2007/10
Y1 - 2007/10
N2 - IL-21, a recently identified member of the common γ-chain (γc) 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 γc 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-7Rα (CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of Th1 and inflammatory cytokines by activated T cells, including IFN-γ, IL-2, tumor necrosis factor-α, granulocyte macrophage colony-stimulating factor, IL-1β 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.
AB - IL-21, a recently identified member of the common γ-chain (γc) 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 γc 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-7Rα (CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of Th1 and inflammatory cytokines by activated T cells, including IFN-γ, IL-2, tumor necrosis factor-α, granulocyte macrophage colony-stimulating factor, IL-1β 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.
KW - Cytotoxic T cell
KW - IL-21
KW - IL-7
KW - Immunotherapy
KW - Tumor immunology
UR - http://www.scopus.com/inward/record.url?scp=34848927882&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34848927882&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxm093
DO - 10.1093/intimm/dxm093
M3 - Article
C2 - 17898044
AN - SCOPUS:34848927882
SN - 0953-8178
VL - 19
SP - 1213
EP - 1221
JO - International Immunology
JF - International Immunology
IS - 10
ER -