Cited by 2,103T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmune Cell Function and Interaction

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Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection

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Wherry, E. John, Ha, Sang-Jun, Kaech, Susan M., Haining, W. Nicholas, Sarkar, Surojit, Kalia, Vandana, Subramaniam, Shruti, Blattman, Joseph N., Barber, Daniel L., Ahmed, Rafi·2007·Immunity

DOI 10.1016/j.immuni.2007.09.006

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Abstract

Chronic viral infections often result in T cell exhaustion. To determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells from chronic infection to functional LCMV-specific effector and memory CD8(+) T cells generated after acute infection. These data showed that exhausted CD8(+) T cells: (1) overexpressed several inhibitory receptors, including PD-1, (2) had major changes in T cell receptor and cytokine signaling pathways, (3) displayed altered expression of genes involved in chemotaxis, adhesion, and migration, (4) expressed a distinct set of transcription factors, and (5) had profound metabolic and bioenergetic deficiencies. T cell exhaustion was progressive, and gene-expression profiling indicated that T cell exhaustion and anergy were distinct processes. Thus, functional exhaustion is probably due to both active suppression and passive defects in signaling and metabolism. These results provide a framework for designing rational immunotherapies during chronic infections.

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Authors: Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R.
Affiliations: Emory University (US)
Dana-Farber Cancer Institute (US)
Corresponding author: Wherry, E. John
Ahmed, Rafi
ORCID: Wherry, E. John
Ha, Sang-Jun
Kaech, Susan M.
Haining, W. Nicholas
Blattman, Joseph N.
Barber, Daniel L.
Ahmed, Rafi
Venue: Immunity
Publisher: Elsevier BV
Published: 2007-10
Volume: 27
Issue: 4
Pages: 670-684
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2007.09.006
OpenAlex: W2040353461
Cited by: 2,103
References: 56
Citations by year: 2026: 110 · 2025: 148 · 2024: 140 · 2023: 144 · 2022: 139 · 2021: 180 · 2020: 161 · 2019: 138 · 2018: 119 · 2017: 102 · 2016: 112 · 2015: 116 · 2014: 88 · 2013: 83 · 2012: 80
FWCI: 19.12
Type: journal article
Language: en
Update notices: erratum (2007-11-26)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2116 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI071309, AI 30048, R01AI071309)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: CD8+ T cell exhaustion, chronic viral infection, lymphocytic choriomeningitis virus, PD-1, inhibitory receptors, T cell receptor signaling, cytokine signaling, T cell metabolism, bioenergetics, T cell migration, transcription factors, T cell anergy, gene expression profiling, immunotherapy
MeSH terms: Animals, Cell Differentiation, Chronic Disease, Female, Flow Cytometry, Immunologic Memory, Lymphocyte Activation, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Molecular Sequence Data, Phenotype, Virus Diseases, Gene Expression, Clonal Anergy, CD8-Positive T-Lymphocytes, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice

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Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection

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