title: T Cell Fate at the Single-Cell Level.
abstract: T cell responses display two key characteristics. First, a small population of epitope-specific naive T cells expands by several orders of magnitude. Second, the T cells within this proliferating population take on diverse functional and phenotypic properties that determine their ability to exert effector functions and contribute to T cell memory. Recent technological advances in lineage tracing allow us for the first time to study these processes in vivo at single-cell resolution. Here, we summarize resulting data demonstrating that although epitope-specific T cell responses are reproducibly similar at the population level, expansion potential and diversification patterns of the offspring derived from individual T cells are highly variable during both primary and recall immune responses. In spite of this stochastic response variation, individual memory T cells can serve as adult stem cells that provide robust regeneration of an epitope-specific tissue through population averaging. We discuss the relevance of these findings for T cell memory formation and clinical immunotherapy.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 München, Germany; email: veit.buchholz@tum.de , dirk.busch@tum.de.
authors.forename: Veit R
authors.initials: VR
authors.lastname: Buchholz
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute (NKI), 1066 CX Amsterdam, The Netherlands; email: t.schumacher@nki.nl.
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 München, Germany; email: veit.buchholz@tum.de , dirk.busch@tum.de.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
mesh_terms: D053687:Adult Stem Cells / Q000276:immunology*; D000818:Animals; D044822:Biodiversity; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018864:Cultural Diversity; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D059010:Single-Cell Analysis / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte
keywords: T cell differentiation; T cell memory; immunotherapy; robustness; stemness; stochasticity