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Towards a unified model of naive T cell dynamics across the lifespan
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348855/ https://www.ncbi.nlm.nih.gov/pubmed/35678373 http://dx.doi.org/10.7554/eLife.78168 |
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author | Rane, Sanket Hogan, Thea Lee, Edward Seddon, Benedict Yates, Andrew J |
author_facet | Rane, Sanket Hogan, Thea Lee, Edward Seddon, Benedict Yates, Andrew J |
author_sort | Rane, Sanket |
collection | PubMed |
description | 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 use multiple modelling and experimental approaches 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. |
format | Online Article Text |
id | pubmed-9348855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-93488552022-08-04 Towards a unified model of naive T cell dynamics across the lifespan Rane, Sanket Hogan, Thea Lee, Edward Seddon, Benedict Yates, Andrew J eLife Computational and Systems Biology 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 use multiple modelling and experimental approaches 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. eLife Sciences Publications, Ltd 2022-06-09 /pmc/articles/PMC9348855/ /pubmed/35678373 http://dx.doi.org/10.7554/eLife.78168 Text en © 2022, Rane, Hogan et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Rane, Sanket Hogan, Thea Lee, Edward Seddon, Benedict Yates, Andrew J Towards a unified model of naive T cell dynamics across the lifespan |
title | Towards a unified model of naive T cell dynamics across the lifespan |
title_full | Towards a unified model of naive T cell dynamics across the lifespan |
title_fullStr | Towards a unified model of naive T cell dynamics across the lifespan |
title_full_unstemmed | Towards a unified model of naive T cell dynamics across the lifespan |
title_short | Towards a unified model of naive T cell dynamics across the lifespan |
title_sort | towards a unified model of naive t cell dynamics across the lifespan |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348855/ https://www.ncbi.nlm.nih.gov/pubmed/35678373 http://dx.doi.org/10.7554/eLife.78168 |
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