Towards a unified model of naive T cell dynamics across the lifespan
- Columbia University, United States
- University College London, United Kingdom
- 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
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
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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Towards a unified model of naive T cell dynamics across the lifespan
eLife 11:e78168.
https://doi.org/10.7554/eLife.78168
