Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels
- Hunter College, City University of New York, United States
- University College London, United Kingdom
- University of Glasgow, United Kingdom
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.
Article and author information
Author details
Funding
National Institutes of Health (R01 AI093870)
- Andrew J Yates
Arthritis Research UK
- Andrew J Yates
Medical Research Council (MC-PC-13055)
- Thea Hogan
- Benedict Seddon
National Science Foundation (1548123)
- Graeme Gossel
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 experiments were performed in accordance with UK Home Office regulations, project license number PPL70-8310.
Copyright
© 2017, Gossel 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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Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels
eLife 6:e23013.
https://doi.org/10.7554/eLife.23013
Further reading
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- Computational and Systems Biology
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Mathematical modeling reveals that long-term immunological memory is maintained in a manner that is even more dynamic than previously thought.
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