Cytomegalovirus Infection: A Driving Force in Human T Cell Immunosenescence

KOCH, SVEN; LARBI, ANIS; ÖZCELIK, DENNIS; SOLANA, RAFAEL; GOUTTEFANGEAS, CÉCILE; ATTIG, SEBASTIAN; WIKBY, ANDERS; STRINDHALL, JAN; FRANCESCHI, CLAUDIO; PAWELEC, GRAHAM

doi:10.1196/annals.1396.043

Cited by 242Cytomegalovirus and herpesvirus researchHerpesvirus Infections and TreatmentsViral-associated cancers and disorders

Cytomegalovirus Infection: A Driving Force in Human T Cell Immunosenescence

KOCH, SVEN, LARBI, ANIS, ÖZCELIK, DENNIS, SOLANA, RAFAEL, GOUTTEFANGEAS, CÉCILE, ATTIG, SEBASTIAN, WIKBY, ANDERS, STRINDHALL, JAN +2 more·2007·Annals of the New York Academy of Sciences

DOI 10.1196/annals.1396.043

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Abstract

Abstract: The human immune system evolved to defend the organism against pathogens, but is clearly less well able to do so in the elderly, resulting in greater morbidity and mortality due to infectious disease in old people, and higher healthcare costs. Many age‐associated immune alterations have been reported over the years, of which probably the changes in T cell immunity, often manifested dramatically as large clonal expansions of cells of limited antigen specificity together with a marked shrinkage of the T cell antigen receptor repertoire, are the most notable. It has recently emerged that the common herpesvirus, cytomegalovirus (CMV), which establishes persistent, life‐long infection, usually asymptomatically, may well be the driving force behind clonal expansions and altered phenotypes and functions of CD8 cells seen in most old people. In those few who are not CMV‐infected, another even more common herpesvirus, the Epstein‐Barr virus, appears to have the same effect. These virus‐driven changes are less marked in “successfully aged” centenarians, but most marked in people whom longitudinal studies have shown to be at higher risk of death, that is, those possessing an “immune risk profile” (IRP) characterized by an inverted CD4:8 ratio (caused by the accumulation primarily of CD8+ CD28− cells). These findings support the hypothesis that persistent herpesviruses, especially CMV, act as chronic antigenic stressors and play a major causative role in immunosenescence and associated mortality.

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Classifying these cells as 'senescent' is subject to debate, and is dependent on what constitutes the definition of senescence.
“Classifying these cells as “senescent” however is subject to debate, and is dependent on what constitutes the definition of senescence (e.g., loss or expression of key cell-surface molecules, functional capacity, such as the ability to proliferate, produce cytokines and kill targets, or telomere length) (Koch et al. 2007; Pawelec 2013).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Koch et al. 2007

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Authors: KOCH, S., LARBI, A., ÖZCELIK, D., SOLANA, R., GOUTTEFANGEAS, C., ATTIG, S., WIKBY, A., STRINDHALL, J., FRANCESCHI, C., & PAWELEC, G.
Affiliations: University of Tübingen (DE)
Universidad de Córdoba (CO)
Jönköping University (SE)
Istituto delle Scienze Neurologiche di Bologna (IT)
Corresponding author: PAWELEC, GRAHAM
ORCID: KOCH, SVEN
LARBI, ANIS
ÖZCELIK, DENNIS
SOLANA, RAFAEL
GOUTTEFANGEAS, CÉCILE
FRANCESCHI, CLAUDIO
PAWELEC, GRAHAM
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2007-10
Volume: 1114
Issue: 1
Pages: 23-35
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1196/annals.1396.043
OpenAlex: W2009730316
Cited by: 242
References: 57
Citations by year: 2026: 4 · 2025: 2 · 2024: 9 · 2023: 8 · 2022: 11 · 2021: 17 · 2020: 9 · 2019: 13 · 2018: 14 · 2017: 17 · 2016: 12 · 2015: 16 · 2014: 13 · 2013: 17 · 2012: 13
FWCI: 1.65
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 31 d)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Funders: European Commission
Topics: Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords: cytomegalovirus infection, immunosenescence, T cell clonal expansion, CD8+ T cells, CD4/CD8 ratio, CD28-negative T cells, Epstein-Barr virus, centenarians, herpesvirus, aging, mortality
MeSH terms: Cytomegalovirus Infections, Cytomegalovirus, Humans, T-Lymphocyte Subsets, Cellular Senescence, CD8-Positive T-Lymphocytes

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Cytomegalovirus Infection: A Driving Force in Human T Cell Immunosenescence

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