Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rane, Sanket, Hogan, Thea, Lee, Edward, Seddon, Benedict, Yates, Andrew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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
_version_ 1784762003854721024
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
work_keys_str_mv AT ranesanket towardsaunifiedmodelofnaivetcelldynamicsacrossthelifespan
AT hoganthea towardsaunifiedmodelofnaivetcelldynamicsacrossthelifespan
AT leeedward towardsaunifiedmodelofnaivetcelldynamicsacrossthelifespan
AT seddonbenedict towardsaunifiedmodelofnaivetcelldynamicsacrossthelifespan
AT yatesandrewj towardsaunifiedmodelofnaivetcelldynamicsacrossthelifespan