Cytotoxic T cells swarm by homotypic chemokine signalling

  1. Jorge Luis Galeano Niño
  2. Sophie V Pageon
  3. Szun S Tay
  4. Feyza Colakoglu
  5. Daryan Kempe
  6. Jack Hywood
  7. Jessica K Mazalo
  8. James Cremasco
  9. Matt A Govendir
  10. Laura F Dagley
  11. Kenneth Hsu
  12. Simone Rizzetto
  13. Jerzy Zieba
  14. Gregory Rice
  15. Victoria Prior
  16. Geraldine M O'Neill
  17. Richard J Williams
  18. David R Nisbet
  19. Belinda Kramer
  20. Andrew I Webb
  21. Fabio Luciani
  22. Mark N Read
  23. Maté Biro  Is a corresponding author
  1. University of New South Wales, Australia
  2. The Walter and Eliza Hall Institute of Medical Research, Australia
  3. The Children's Hospital at Westmead, Australia
  4. University of Waterloo, Canada
  5. Kids Research, Australia
  6. Deakin University, Australia
  7. Australian National University, Australia
  8. 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

  1. Jorge Luis Galeano Niño

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Sophie V Pageon

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1701-5551
  3. Szun S Tay

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0186-8154
  4. Feyza Colakoglu

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Daryan Kempe

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Jack Hywood

    Sydney Medical School, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Jessica K Mazalo

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. James Cremasco

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Matt A Govendir

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Laura F Dagley

    Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4171-3712
  11. Kenneth Hsu

    Children's Cancer Research Unit, The Children's Hospital at Westmead, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  12. Simone Rizzetto

    Sydney Medical School, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3881-8759
  13. Jerzy Zieba

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Gregory Rice

    Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Canada
    Competing interests
    The authors declare that no competing interests exist.
  15. Victoria Prior

    Children's Cancer Research Unit, Kids Research, Westmead, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2285-5398
  16. Geraldine M O'Neill

    Children's Cancer Research Unit, The Children's Hospital at Westmead, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. Richard J Williams

    School of Medicine, Deakin University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  18. David R Nisbet

    Advanced Biomaterials Lab, Research School of Engineering, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  19. Belinda Kramer

    Children's Cancer Research Unit, The Children's Hospital at Westmead, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  20. Andrew I Webb

    Advanced Technology and Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  21. Fabio Luciani

    School of Medical Sciences, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  22. Mark N Read

    Charles Perkins Centre, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  23. Maté Biro

    EMBL Australia, Single Molecule Science node, University of New South Wales, Sydney, Australia
    For correspondence
    m.biro@unsw.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5852-3726

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.

Reviewing Editor

  1. Satyajit Rath, Indian Institute of Science Education and Research (IISER), India

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).

Version history

  1. Received: March 2, 2020
  2. Accepted: September 27, 2020
  3. Accepted Manuscript published: October 13, 2020 (version 1)
  4. Accepted Manuscript updated: October 16, 2020 (version 2)
  5. Version of Record published: November 16, 2020 (version 3)

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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  1. Jorge Luis Galeano Niño
  2. Sophie V Pageon
  3. Szun S Tay
  4. Feyza Colakoglu
  5. Daryan Kempe
  6. Jack Hywood
  7. Jessica K Mazalo
  8. James Cremasco
  9. Matt A Govendir
  10. Laura F Dagley
  11. Kenneth Hsu
  12. Simone Rizzetto
  13. Jerzy Zieba
  14. Gregory Rice
  15. Victoria Prior
  16. Geraldine M O'Neill
  17. Richard J Williams
  18. David R Nisbet
  19. Belinda Kramer
  20. Andrew I Webb
  21. Fabio Luciani
  22. Mark N Read
  23. Maté Biro
(2020)
Cytotoxic T cells swarm by homotypic chemokine signalling
eLife 9:e56554.
https://doi.org/10.7554/eLife.56554

Share this article

https://doi.org/10.7554/eLife.56554

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