title: Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux.
abstract: Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCMpool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCMcells in vivo using stable isotope labeling with heavy water. The data indicate that TSCMcells in both young and elderly subjects are maintained by ongoing proliferation. In line with this finding, TSCMcells displayed limited telomere length erosion coupled with high expression levels of active telomerase and Ki67. Collectively, these observations show that TSCMcells exist in a state of perpetual flux throughout the human lifespan.
authors.affiliation: Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
authors.forename: Raya
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Laureline
authors.initials: L
authors.lastname: Roger
authors.affiliation: Department of Medicine, St. Mary's Hospital, Imperial College London, London W2 1PG, UK.
authors.forename: Pedro
authors.initials: P
authors.lastname: Costa Del Amo
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Miners
authors.affiliation: Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Rhiannon E
authors.initials: RE
authors.lastname: Jones
authors.affiliation: Department of Medicine, St. Mary's Hospital, Imperial College London, London W2 1PG, UK.
authors.forename: Lies
authors.initials: L
authors.lastname: Boelen
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013 Paris, France; INSERM U1135, CIMI-Paris, 75013 Paris, France.
authors.forename: Tinhinane
authors.initials: T
authors.lastname: Fali
authors.affiliation: Department of Medicine, St. Mary's Hospital, Imperial College London, London W2 1PG, UK.
authors.forename: Marjet
authors.initials: M
authors.lastname: Elemans
authors.affiliation: Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013 Paris, France; INSERM U1135, CIMI-Paris, 75013 Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Appay
authors.affiliation: Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Baird
authors.affiliation: Department of Medicine, St. Mary's Hospital, Imperial College London, London W2 1PG, UK.
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: priced6@cardiff.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK; St. George's University Hospitals National Health Service Foundation Trust, Blackshaw Road, London SW17 0QT, UK. Electronic address: macallan@sgul.ac.uk.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Macallan
authors.affiliation: Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: ladellk@gmail.com.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
mesh_terms: D056704:Adaptive Immunity; D019070:Cell Lineage / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics; D000066673:Cell Self Renewal / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007553:Isotope Labeling; D019394:Ki-67 Antigen / Q000235:genetics; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019098:Telomerase / Q000235:genetics
chemical_list: D019394:Ki-67 Antigen; D019098:Telomerase
keywords: CD4(+) T cells; CD8(+) T cells; adaptive immunity; in vivo heavy water labeling; memory T cell maintenance; memory T cells; proliferation; stem cell-like memory T cells; telomerase activity; telomere length