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Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
Published on: December 12, 2014
Cytotoxic T cells swarm by homotypic chemokine signalling
Jorge Luis Galeano Niño1,2, Sophie V Pageon1,2, Szun S Tay1,2
1EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia.
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.
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