Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels
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 the maintenance of memory compartments. Here, we c...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/23013 |
| _version_ | 1811227990008266752 |
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| author | Graeme Gossel Thea Hogan Daniel Cownden Benedict Seddon Andrew J Yates |
| author_facet | Graeme Gossel Thea Hogan Daniel Cownden Benedict Seddon Andrew J Yates |
| author_sort | Graeme Gossel |
| collection | DOAJ |
| description | 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 the 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. |
| first_indexed | 2024-04-12T09:50:58Z |
| format | Article |
| id | doaj.art-79ecc5d314574e268efe041f59d37023 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:50:58Z |
| publishDate | 2017-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-79ecc5d314574e268efe041f59d370232022-12-22T03:37:50ZengeLife Sciences Publications LtdeLife2050-084X2017-03-01610.7554/eLife.23013Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levelsGraeme Gossel0Thea Hogan1Daniel Cownden2Benedict Seddon3Andrew J Yates4https://orcid.org/0000-0003-4606-4483Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences University of Glasgow, Glasgow, United Kingdom; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United StatesInstitute of Immunity and Transplantation, University College London, London, United KingdomInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences University of Glasgow, Glasgow, United KingdomInstitute of Immunity and Transplantation, University College London, London, United KingdomInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences University of Glasgow, Glasgow, United KingdomCharacterising 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 the 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.https://elifesciences.org/articles/23013T cell homeostasisBrdU labellingKi67memory T cellsmathematical modelling |
| spellingShingle | Graeme Gossel Thea Hogan Daniel Cownden Benedict Seddon Andrew J Yates Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels eLife T cell homeostasis BrdU labelling Ki67 memory T cells mathematical modelling |
| title | Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels |
| title_full | Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels |
| title_fullStr | Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels |
| title_full_unstemmed | Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels |
| title_short | Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels |
| title_sort | memory cd4 t cell subsets are kinetically heterogeneous and replenished from naive t cells at high levels |
| topic | T cell homeostasis BrdU labelling Ki67 memory T cells mathematical modelling |
| url | https://elifesciences.org/articles/23013 |
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