title: Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels.
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 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.
authors.affiliation: Institute 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 States.
authors.forename: Graeme
authors.initials: G
authors.lastname: Gossel
authors.affiliation: Institute of Immunity and Transplantation, University College London, London, United Kingdom.
authors.forename: Thea
authors.initials: T
authors.lastname: Hogan
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences University of Glasgow, Glasgow, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cownden
authors.affiliation: Institute of Immunity and Transplantation, University College London, London, United Kingdom.
authors.forename: Benedict
authors.initials: B
authors.lastname: Seddon
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary & Life Sciences University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrew J
authors.identifier: 0000-0003-4606-4483
authors.initials: AJ
authors.lastname: Yates
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*
keywords: BrdU labelling; Ki67; T cell homeostasis; computational biology; immunology; mathematical modelling; memory T cells; mouse; systems biology