title: Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells.
abstract: Maintenance of immunological memory has been proposed to rely on stem-cell-like lymphocytes. However, data supporting this hypothesis are focused on the developmental potential of lymphocyte populations and are thus insufficient to establish the functional hallmarks of stemness. Here, we investigated self-renewal capacity and multipotency of individual memory lymphocytes by in vivo fate mapping of CD8(+) T cells and their descendants across three generations of serial single-cell adoptive transfer and infection-driven re-expansion. We found that immune responses derived from single naive T (Tn) cells, single primary, and single secondary central memory T (Tcm) cells reached similar size and phenotypic diversity, were subjected to comparable stochastic variation, and could ultimately reconstitute immunocompetence against an otherwise lethal infection with the bacterial pathogen Listeria monocytogenes. These observations establish that adult tissue stem cells reside within the CD62L(+) Tcm cell compartment and highlight the promising therapeutic potential of this immune cell subset.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Graef
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany.
authors.forename: Veit R
authors.initials: VR
authors.lastname: Buchholz
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany; Focus Group "Clinical Cell Processing and Purification," Institute for Advanced Study, TUM, Munich 81675, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stemberger
authors.affiliation: Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; BioQuant Center, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Flossdorf
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany.
authors.forename: Lynette
authors.initials: L
authors.lastname: Henkel
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany; Clinical Cooperation Groups "Antigen-specific Immunotherapy" and "Immune-Monitoring," Helmholtz Center Munich (Neuherberg), TUM, Munich 81675, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.affiliation: Institute for Virology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine Universität, Düsseldorf 40225, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Drexler
authors.affiliation: Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; BioQuant Center, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfer
authors.affiliation: Focus Group "Clinical Cell Processing and Purification," Institute for Advanced Study, TUM, Munich 81675, Germany; Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich 81675, Germany; Focus Group "Clinical Cell Processing and Purification," Institute for Advanced Study, TUM, Munich 81675, Germany; Clinical Cooperation Groups "Antigen-specific Immunotherapy" and "Immune-Monitoring," Helmholtz Center Munich (Neuherberg), TUM, Munich 81675, Germany; German Center for Infection Research (DZIF), Munich 81675, Germany. Electronic address: dirk.busch@tum.de.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
mesh_terms: D053687:Adult Stem Cells / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D007121:Immunocompetence / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D019041:L-Selectin / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D019041:L-Selectin