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T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections.

  • Utzschneider DT Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
  • Charmoy M Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
  • Chennupati V Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
  • Pousse L Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
  • Ferreira DP Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
  • Calderon-Copete S Lausanne Genomic Technologies Facility (LGTF), University of Lausanne, 1015 Lausanne, Switzerland.
  • Danilo M Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland.
  • Alfei F Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
  • Hofmann M Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, University of Freiburg, 79106 Freiburg, Germany.
  • Wieland D 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.
  • Pradervand S Lausanne Genomic Technologies Facility (LGTF), University of Lausanne, 1015 Lausanne, Switzerland.
  • Thimme R Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie, University of Freiburg, 79106 Freiburg, Germany.
  • Zehn D Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland. Electronic address: dietmar.zehn@tum.de.
  • Held W Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 1066 Epalinges, Switzerland. Electronic address: werner.held@unil.ch.
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  • 2016-08-18
Published in:
  • Immunity. - 2016
LCMV
PD-1
T cell exhaustion
T cell memory
Tcf1
chronic infection
differentiation of cytotoxic T cells
Adult
Animals
Antigens, CD
CD8-Positive T-Lymphocytes
Cell Proliferation
Cells, Cultured
Cellular Senescence
Chronic Disease
Female
Hepacivirus
Hepatitis C, Chronic
Humans
Immunologic Memory
Immunotherapy
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Middle Aged
Programmed Cell Death 1 Receptor
T Cell Transcription Factor 1
Transcriptome
English 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.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/289163
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