Division of Tumor Biology and Immunology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, 1066 CX Amsterdam, the Netherlands.
Division of Tumor Biology and Immunology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, 1066 CX Amsterdam, the Netherlands.
Immunity. 2017 Nov 21;47(5):848-861.e5. doi: 10.1016/j.immuni.2017.10.009. Epub 2017 Nov 7.
CD4 T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4 T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4 T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. Key features included downregulation of PD-1 and other coinhibitory receptors that impede CTL activity, and increased motility and migration capacities. "Helped" CTLs acquired chemokine receptors that helped them reach their tumor target tissue and metalloprotease activity that enabled them to invade into tumor tissue. A very large part of the "help" program was instilled in CD8 T cells via CD27 costimulation. The help program thus enhances specific CTL effector functions in response to vaccination or a virus infection.
CD4 T 细胞通过未知的分子机制优化细胞毒性 T 细胞 (CTL) 的反应幅度和质量。我们在此介绍了抗癌疫苗接种或病毒感染后 CD4 T 细胞辅助对 CTL 产生的转录组变化。基因表达特征表明，在启动阶段，CD4 T 细胞辅助优化了 CTL 表达细胞毒性效应分子和许多其他功能，从而确保了 CTL 整个生命周期的功效。关键特征包括下调 PD-1 和其他抑制性受体，这些受体阻碍 CTL 活性，以及增加运动和迁移能力。“受辅助”的 CTL 获得趋化因子受体，帮助它们到达肿瘤靶组织，以及金属蛋白酶活性，使它们能够侵入肿瘤组织。通过 CD27 共刺激，“帮助”程序的很大一部分被注入 CD8 T 细胞。因此，该帮助程序增强了针对疫苗接种或病毒感染的特定 CTL 效应功能。
