Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels

Gossel, G., Hogan, T., Cownden, D., Seddon, B. and Yates, A. J. (2017) Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels. eLife, 6, e23013. (doi: 10.7554/eLife.23013) (PMID:28282024) (PMCID:PMC5426903)

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Abstract

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

Item Type:Articles
Keywords:Computational biology, immunology, mouse, systems biology.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cownden, Dr Daniel and Yates, Professor Andrew and Gossel, Dr Graeme
Authors: Gossel, G., Hogan, T., Cownden, D., Seddon, B., and Yates, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2017 Grossel et al.
First Published:First published in eLife 6: e23013
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
673361Modeling the development, age structure and maintenance of T cell populationsAndrew YatesNational Institute of Health (USA) (NIH(US))R01AI093870III -IMMUNOLOGY