Towards a unified model of naive T cell dynamics across the lifespan

  1. Sanket Rane
  2. Thea Hogan
  3. Edward Lee
  4. Benedict Seddon  Is a corresponding author
  5. Andrew J Yates  Is a corresponding author
  1. Columbia University, United States
  2. University College London, United Kingdom
  3. Yale University, United States

Abstract

Naive CD4 and CD8 T cells are cornerstones of adaptive immunity, but the dynamics of their establishment early in life and how their kinetics change as they mature following release from the thymus are poorly understood. Further, due to the diverse signals implicated in naive T cell survival, it has been a long-held and conceptually attractive view that they are sustained by active homeostatic control as thymic activity wanes. Here we employ multiple experimental systems to identify a unified model of naive CD4 and CD8 T cell population dynamics in mice, across their lifespan. We infer that both subsets divide rarely and progressively increase their survival capacity with cell age. Strikingly, this simple model is able to describe naive CD4 T cell dynamics throughout life. In contrast, we find that newly generated naive CD8 T cells are lost more rapidly during the first 3-4 weeks of life, likely due to increased recruitment into memory. We find no evidence for elevated division rates in neonates, or for feedback regulation of naive T cell numbers at any age. We show how confronting mathematical models with diverse datasets can reveal a quantitative and remarkably simple picture of naive T cell dynamics in mice from birth into old age.

Data availability

All code and data used in this study are available at https://github.com/sanketrane/T_cell_dynamics_birth-death

Article and author information

Author details

  1. Sanket Rane

    Department of Pathology and Cell Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Thea Hogan

    Institute of Immunity and Transplantation, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Edward Lee

    Department of Laboratory Medicine, Yale University, Newhaven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Benedict Seddon

    Institute of Immunity and Transplantation, University College London, London, United Kingdom
    For correspondence
    benedict.seddon@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4352-3373
  5. Andrew J Yates

    Department of Pathology and Cell Biology, Columbia University, New York, United States
    For correspondence
    andrew.yates@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4606-4483

Funding

National Institutes of Health (R01AI093870)

  • Andrew J Yates

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 of the animals were handled according to UK home office regulations (licence PPL PP2330953) and institutional animal care and use committee (IACUC) protocols at University College London

Reviewing Editor

  1. Gabrielle T Belz, The University of Queensland, Australia

Publication history

  1. Preprint posted: January 8, 2022 (view preprint)
  2. Received: February 25, 2022
  3. Accepted: June 8, 2022
  4. Accepted Manuscript published: June 9, 2022 (version 1)
  5. Accepted Manuscript updated: June 10, 2022 (version 2)
  6. Version of Record published: August 3, 2022 (version 3)

Copyright

© 2022, Rane 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. Sanket Rane
  2. Thea Hogan
  3. Edward Lee
  4. Benedict Seddon
  5. Andrew J Yates
(2022)
Towards a unified model of naive T cell dynamics across the lifespan
eLife 11:e78168.
https://doi.org/10.7554/eLife.78168

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