IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells.
IL-21, a recently identified member of the common gamma-chain (gammac) 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 gammac 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-7Ralpha (CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of T(h)1 and inflammatory cytokines by activated T cells, including IFN-gamma, IL-2, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, IL-1beta 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.
Liu
Shujuan
S
Department of Melanoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Lizée
Gregory
G
Lou
Yanyan
Y
Liu
Chengwen
C
Overwijk
Willem W
WW
Wang
Gang
G
Hwu
Patrick
P
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015851:Interleukin-7 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D000098546:Interleukin-21; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D016207:Cytokines; D015851:Interleukin-7; D007378:Interleukins; D037181:Lectins, C-Type; D020395:Receptors, Interleukin-7; D000098546:Interleukin-21; D000099192:CD69 Antigens; C415350:interleukin-7 receptor, alpha chain