Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex

  1. Daniel Blumenthal  Is a corresponding author
  2. Vidhi Chandra
  3. Lyndsay Avery
  4. Janis K Burkhardt  Is a corresponding author
  1. The Children's Hospital of Philadelphia Research Institute, United States
  2. Children's Hospital of Philadelphia Research Institute, United States

Abstract

T cell activation by dendritic cells (DCs) involves forces exerted by the T cell actin cytoskeleton, which are opposed by the cortical cytoskeleton of the interacting APC. During an immune response, DCs undergo a maturation process that optimizes their ability to efficiently prime naïve T cells. Using atomic force microscopy, we find that during maturation, DC cortical stiffness increases via a process that involves actin polymerization. Using stimulatory hydrogels and DCs expressing mutant cytoskeletal proteins, we find that increasing stiffness lowers the agonist dose needed for T cell activation. CD4+ T cells exhibit much more profound stiffness-dependency than CD8+ T cells. Finally, stiffness responses are most robust when T cells are stimulated with pMHC rather than anti-CD3ε, consistent with a mechanosensing mechanism involving receptor deformation. Taken together, our data reveal that maturation-associated cytoskeletal changes alter the biophysical properties of DCs, providing mechanical cues that costimulate T cell activation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Daniel Blumenthal

    Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia Research Institute, Philadelphia, United States
    For correspondence
    daniel.blumenthal.chop@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
  2. Vidhi Chandra

    Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3642-2144
  3. Lyndsay Avery

    Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Janis K Burkhardt

    Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute, Philadelphia, United States
    For correspondence
    jburkhar@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8176-1375

Funding

National Institute of General Medical Sciences (GM104867)

  • Janis K Burkhardt

National Institute of Allergy and Infectious Diseases (AI32828)

  • Janis K Burkhardt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Michael L Dustin, University of Oxford, United Kingdom

Ethics

Animal experimentation: All studies, breeding and maintenance of animals was performed under AnimalCare and Use Protocol #667, as approved by The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee.

Version history

  1. Received: February 14, 2020
  2. Accepted: July 27, 2020
  3. Accepted Manuscript published: July 27, 2020 (version 1)
  4. Version of Record published: August 10, 2020 (version 2)

Copyright

© 2020, Blumenthal 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. Daniel Blumenthal
  2. Vidhi Chandra
  3. Lyndsay Avery
  4. Janis K Burkhardt
(2020)
Mouse T cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex
eLife 9:e55995.
https://doi.org/10.7554/eLife.55995

Share this article

https://doi.org/10.7554/eLife.55995

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