Cytotoxic T Cells swarm by homotypic chemokine signalling
- EMBL Australia, Australia
- University of New South Wales, Australia
- The University of Sydney, Australia
- The Walter and Eliza Hall Institute of Medical Research, Australia
- The Children's Hospital at Westmead, Australia
- University of Waterloo, Canada
- Kids Research, Australia
- Deakin University, Australia
- Australian National University, Australia
- University of 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files with extensive statistical information have been provided for all figures containing bar, box or violin plots. Complete transcriptomics and secretomics data are available in Supplementary Files 1 and 2 respectively. Custom code and notes are available at http://www.matebiro.com/software/motilisim
Article and author information
Author details
Funding
National Sciences and Engineering Research Council Canada (RGPIN 50503-10477 and 50503-10476)
- Gregory Rice
National Health and Medical Research Council (GNT1135687)
- David R Nisbet
University of Sydney CoE in Advanced Food Enginomics
- Mark N Read
EMBL Australia
- Maté Biro
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal breeding and experimentation were conducted in accordance with New South Wales state and Australian federal laws and animal ethics protocols overseen and approved by the University of New South Wales Animal Care and Ethics Committee (ACEC) under protocols 16/83B and 19/133B.
Human subjects: Human peripheral blood mononuclear cells (PBMCs) were obtained from healthy donors after informed consent and were used in experiments under a Human Research Ethics Committee (HREC) approved protocol (Sydney Children's Hospitals Network, LNR/13/SCHN/241).
Copyright
© 2020, Galeano Niño et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cytotoxic T Cells swarm by homotypic chemokine signalling
eLife 9:e56554.
https://doi.org/10.7554/eLife.56554
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