title: T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.
abstract: Chronic infections promote the terminal differentiation (or "exhaustion") of T cells and are thought to preclude the formation of memory T cells. In contrast, we discovered a small subpopulation of virus-specific CD8(+) T cells that sustained the T cell response during chronic infections. These cells were defined by, and depended on, the expression of the transcription factor Tcf1. Transcriptome analysis revealed that this population shared key characteristics of central memory cells but lacked an effector signature. Unlike conventional memory cells, Tcf1-expressing T cells displayed hallmarks of an "exhausted" phenotype, including the expression of inhibitory receptors such as PD-1 and Lag-3. This population was crucial for the T cell expansion that occurred in response to inhibitory receptor blockade during chronic infection. These findings identify a memory-like T cell population that sustains T cell responses and is a prime target for therapeutic interventions to improve the immune response in chronic infections.
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Utzschneider
authors.affiliation: Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Charmoy
authors.affiliation: Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Chennupati
authors.affiliation: Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Laurène
authors.initials: L
authors.lastname: Pousse
authors.affiliation: Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Daniela Pais
authors.initials: DP
authors.lastname: Ferreira
authors.affiliation: Lausanne Genomic Technologies Facility (LGTF), University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Calderon-Copete
authors.affiliation: Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Maxime
authors.initials: M
authors.lastname: Danilo
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Alfei
authors.affiliation: Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Hofmann
authors.affiliation: Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, University of Freiburg, 79106 Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wieland
authors.affiliation: Lausanne Genomic Technologies Facility (LGTF), University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradervand
authors.affiliation: Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland. Electronic address: dietmar.zehn@tum.de.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.affiliation: Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland. Electronic address: werner.held@unil.ch.
authors.forename: Werner
authors.initials: W
authors.lastname: Held
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D051822:T Cell Transcription Factor 1 / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D051822:T Cell Transcription Factor 1; D000093322:Lymphocyte Activation Gene 3 Protein
keywords: LCMV; PD-1; T cell exhaustion; T cell memory; Tcf1; chronic infection; differentiation of cytotoxic T cells