Tianjin Third Central Hospital Affiliated to Tianjin Medical University, Tianjin Key Laboratory of Artificial Cells, Tianjin 300170, China.
Cell Immunol. 2011;271(1):118-23. doi: 10.1016/j.cellimm.2011.06.013. Epub 2011 Jun 23.
Interaction of costimulatory molecules and their receptors is crucial for tumor lysate-pulsed dendritic cells (sensitized DC, sDC) to promote T cell activation, clonal expansion and its antitumor immunity. To augment the costimulatory signal may regulate the interaction between DC and cytotoxic T lymphocyte (CTL) and consequently enhance the antitumor response. The costimulatory ligand and receptor pair of 4-1BB/4-1BBL is one of the main factors in the costimulation of CTL. We explored the adjuvant role of a recombinant human 4-1BBL extracellular domain (ex4-1BBL) in modulating CTL activation induced by HepG2 antigen-loaded DC (sDC). The augment effects of sDC in combination with ex4-1BBL on the proliferation, activation, cell survival and cytotoxicity against HepG2 cells of CTL were examined. In the presence of ex4-1BBL, sDC exhibited markedly augmented effects on the above four functions of CTL. These results demonstrate that ex4-1BBL plays an important role in the costimulation pathway for DC-mediated CTL's activation, which might be a useful adjuvant factor for DC-based cancer biotherapy.
共刺激分子及其受体的相互作用对于肿瘤裂解物脉冲树突状细胞（致敏 DC，sDC）促进 T 细胞激活、克隆扩增及其抗肿瘤免疫至关重要。增强共刺激信号可能调节 DC 和细胞毒性 T 淋巴细胞（CTL）之间的相互作用，从而增强抗肿瘤反应。4-1BB/4-1BBL 的共刺激配体和受体对是 CTL 共刺激的主要因素之一。我们探讨了重组人 4-1BBL 细胞外结构域（ex4-1BBL）在调节负载 HepG2 抗原的 DC（sDC）诱导的 CTL 激活中的佐剂作用。检测了 sDC 与 ex4-1BBL 联合对 CTL 的增殖、激活、细胞存活和对 HepG2 细胞的细胞毒性的增强作用。在 ex4-1BBL 的存在下，sDC 对 CTL 的上述四种功能表现出明显的增强作用。这些结果表明，ex4-1BBL 在 DC 介导的 CTL 激活的共刺激途径中发挥重要作用，可能是基于 DC 的癌症生物治疗的有用佐剂因子。
