| Literature DB >> 33046212 |
Jorge Luis Galeano Niño1,2, Sophie V Pageon1,2, Szun S Tay1,2, Feyza Colakoglu1,2, Daryan Kempe1,2, Jack Hywood3, Jessica K Mazalo1,2, James Cremasco1,2, Matt A Govendir1,2, Laura F Dagley4,5, Kenneth Hsu6, Simone Rizzetto2,7, Jerzy Zieba2,8, Gregory Rice9, Victoria Prior6,10, Geraldine M O'Neill6,10, Richard J Williams11,12, David R Nisbet11,13, Belinda Kramer6, Andrew I Webb4,5, Fabio Luciani2,7, Mark N Read14, Maté Biro1,2.
Abstract
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.Entities:
Keywords: T cells; cell migration; chemotaxis; computational biology; emergent behaviour; human; immunology; inflammation; mouse; simulations; swarming; systems biology
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Year: 2020 PMID: 33046212 PMCID: PMC7669268 DOI: 10.7554/eLife.56554
Source DB: PubMed Journal: Elife ISSN: 2050-084X Impact factor: 8.140