Cytotoxic T cells swarm by homotypic chemokine signalling

eLife

Belinda Kramer¹  Laura F Dagley²  Richard J Williams²  Jack Hywood²  James Cremasco²  Jerzy Zieba²  Victoria Prior²  Feyza Colakoglu²  Sophie V Pageon²  Mark N Read³  Andrew I Webb⁴  Gregory Rice⁵  Simone Rizzetto⁵  Jorge Luis Galeano Niño⁵  Matt A Govendir⁵  Geraldine M O'Neill⁵  Daryan Kempe⁵  Jessica K Mazalo⁵  Szun S Tay⁵  Maté Biro⁶  Fabio Luciani⁶  Kenneth Hsu⁷  David R Nisbet⁸ 

[1]Department of Medical Biology, University of Melbourne, Melbourne, Australia

[2]School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia

[3]The Kirby Institute for Infection and Immunity in Society, UNSW, Sydney, Australia

[4]Children's Cancer Research Unit, The Children's Hospital at Westmead, Sydney, Australia

[5]EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia

[6]School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia

[7]Sydney Medical School, The University of Sydney, Sydney, Australia

[8]The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

关键词: T cells;    swarming;    emergent behaviour;    chemotaxis;    cell migration;    simulations;   

DOI  :  10.7554/eLife.56554

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown