EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia.
School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Elife. 2020 Oct 13;9:e56554. doi: 10.7554/eLife.56554.
Cytotoxic T lymphocytes (CTLs) are thought to arrive at target sites either via random search or following signals by other leukocytes. Here, we reveal independent emergent behaviour in CTL populations attacking tumour masses. Primary murine CTLs coordinate their migration in a process reminiscent of the swarming observed in neutrophils. CTLs engaging cognate targets accelerate the recruitment of distant T cells through long-range homotypic signalling, in part mediated via the diffusion of chemokines CCL3 and CCL4. Newly arriving CTLs augment the chemotactic signal, further accelerating mass recruitment in a positive feedback loop. Activated effector human T cells and chimeric antigen receptor (CAR) T cells similarly employ intra-population signalling to drive rapid convergence. Thus, CTLs recognising a cognate target can induce a localised mass response by amplifying the direct recruitment of additional T cells independently of other leukocytes.
细胞毒性 T 淋巴细胞(CTL)被认为可以通过随机搜索或其他白细胞的信号到达靶位。在这里,我们揭示了攻击肿瘤的 CTL 群体中独立的涌现行为。原代鼠 CTL 通过类似于中性粒细胞中观察到的群集的过程协调其迁移。与同源靶标结合的 CTL 通过长程同种型信号加速招募远处的 T 细胞,部分通过趋化因子 CCL3 和 CCL4 的扩散介导。新到达的 CTL 增强趋化信号,在正反馈环中进一步加速群体招募。活化的效应人 T 细胞和嵌合抗原受体(CAR)T 细胞也通过群体内信号传递来驱动快速收敛。因此,识别同源靶标的 CTL 可以通过独立于其他白细胞扩增直接招募额外 T 细胞来诱导局部群体反应。