Ju Seong-A, Park Sang-Min, Lee Sang-Chul, Kwon Byoung S, Kim Byung-Sam
Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
Mol Cells. 2007 Aug 31;24(1):132-8.
4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of CD11c+CD8+ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of IFN- in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the CD11c+CD8+ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, IFN- and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that CD11c+CD8+ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.
4-1BB（CD137）是肿瘤坏死因子受体超家族的成员，在活化的T细胞上表达，与4-1BB配体相互作用或用抗4-1BB单克隆抗体（mAb）进行连接所引发的4-1BB信号传导可共刺激T细胞。已有研究表明，给予抗4-1BB mAb可在小鼠中诱导抗肿瘤免疫，但负责这种免疫的细胞亚群的性质尚不确定。在本研究中，我们发现给携带B16F10黑色素瘤的小鼠施用抗4-1BB mAb可诱导CD11c + CD8 + T细胞显著扩增，同时抑制肺部肿瘤。与接受对照抗体的小鼠相比，用mAb处理的小鼠在其肿瘤组织、脾脏和淋巴结中产生更高水平的干扰素。当CD11c + CD8 + T细胞在体外纯化并重新刺激时，它们产生高水平的Th1细胞因子干扰素和白细胞介素-2，但产生低水平的Th2细胞因子白细胞介素-4和白细胞介素-10。此外，它们高水平表达4-1BB和CD107a，后者是活化的细胞毒性T淋巴细胞的标志物。我们的结果表明，CD11c + CD8 + T细胞在抗4-1BB mAb诱导的抗肿瘤免疫中发挥作用。
