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了细胞毒性T细胞（CTL）反应的大小和质量。我们在此介绍抗癌疫苗接种或病毒感染后CD4 ⁺ T细胞帮助引起的CTL转录组学变化。基因表达特征表明CD4 ⁺在引发优化的CTL期间，T细胞有助于细胞毒性效应分子的表达以及许多其他功能，这些功能确保了CTL在其整个生命周期中的功效。主要特征包括PD-1和其他抑制CTL活性的共抑制受体的下调，以及增加的运动性和迁移能力。“帮助的” CTL获得趋化因子受体，从而帮助它们达到肿瘤靶组织和金属蛋白酶活性，从而使其侵入肿瘤组织。通过CD27共刺激，“帮助”程序的很大一部分被注入到CD8 ⁺ T细胞中。因此，该帮助程序可以响应疫苗接种或病毒感染来增强特定的CTL效应子功能。