Liu Shujuan, Lizée Gregory, Lou Yanyan, Liu Chengwen, Overwijk Willem W, Wang Gang, Hwu Patrick
Department of Melanoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Int Immunol. 2007 Oct;19(10):1213-21. doi: 10.1093/intimm/dxm093.
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.
白细胞介素-21（IL-21）是最近发现的共同γ链（γc）受体细胞因子家族成员，已被证明是先天性和适应性免疫反应的重要调节因子。在本研究中，我们调查了IL-21是否能与另一种γc细胞因子IL-7协同作用，以诱导肿瘤抗原特异性CD8(+) T细胞增强增殖和效应功能。我们的结果表明，IL-21可能通过防止细胞因子诱导的抗原刺激T细胞上IL-7Rα（CD127）下调，从而显著增强IL-7诱导的细胞毒性T细胞扩增。IL-21还极大地增强了活化T细胞产生的Th1和炎性细胞因子，包括干扰素-γ、IL-2、肿瘤坏死因子-α、粒细胞巨噬细胞集落刺激因子、IL-1β和IL-6。最后，将IL-21添加到IL-7培养的细胞毒性T淋巴细胞（CTL）中，通过对肿瘤细胞或抗原脉冲靶细胞的特异性杀伤测定，导致细胞溶解活性水平显著更高。这些结果表明，IL-21可能在调节原发性CD8(+) T细胞反应中与IL-7发挥协同作用，并且可能对癌症免疫治疗具有重要意义。
