Biomarkers of human immunosenescence: impact of cytomegalovirus infection
Abstract
Age-associated failing systemic immunity, loosely termed 'immunosenescence', is thought to contribute to the increased incidence and severity of infectious disease in old people. It would therefore be of great practical as well as academic interest to accurately identify which of the multitude of alterations to immune parameters thus far reported are causally related to a person's clinically unfavourable health status, in order to identify the mechanisms of immune ageing and intervene to restore appropriate immunity. This is an enormous current challenge, as it requires longitudinal studies in a very long-lived species. Circumstantial evidence and longitudinal studies limited to the very elderly have begun to reveal 'immune signatures' or biomarkers of immune ageing consisting not of a single parameter, but clusters of parameters increasingly recognized as an 'immune risk profile', or IRP. Although hinted at many years ago, a marked impact of usually asymptomatic infection with the persistent beta-herpesvirus Cytomegalovirus (CMV) on markers of immunosenescence is now becoming incontrovertible. The fascinating cohabitation of CMV with the human immune system, which commits a very significant fraction of its entire resources to CMV-immunosurveillance, may suggest an early-life benefit from infection, which becomes deleterious for the majority of the population only in later life or under pathological conditions.
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These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.
“These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [45]
Senescent T cells are producers of pro-inflammatory cytokines.
“In addition, they are producers of pro-inflammatory cytokines (17, 18, 41–47).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [45]
CD28 seems a good biomarker of immunosenescence, as suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.
“CD28 seems a good biomarker of immunosenescence, as further suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [45]
Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.
“Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [45]
The loss of CD28 occurs following cell proliferation, according to the observation that CD28− T cells have shorter telomeres than CD28+ cells.
“The loss of CD28 occurs following cell proliferation, according to the observation that the CD28− T cells have shorter telomeres than CD28+ cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [45]
Emerging data suggest that HIV and CMV co-infections interact in a potential negative manner.
“The impact of HIV disease on this process is not known, but emerging data suggest that these co-infections interact in a potential negative manner (41–44).”
From HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group (2012) · cites this paper as [42]
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Self-citationLarge-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging
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Immunosenescence and Cytomegalovirus: where do we stand after a decade?
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Self-citationRudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults
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Self-citationEffect of ageing on CMV-specific CD8 T cells from CMV seropositive healthy donors
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Chen, S., de Craen, A. J. M., Raz, Y., Derhovanessian, E., Vossen, A. C. T. M., Rudi, G. J. W., Pawelec, G., & Maier, A. B. (2012) · Immunity & Ageing · doi:10.1186/1742-4933-9-18 · Cited by 77 · see citing works
Self-citationNKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system
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Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection
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Cytomegalovirus Exposure and Cardiovascular Disease in Kidney Transplant Recipients
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Impact of CMV upon immune aging: facts and fiction
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Self-citationCytomegalovirus Infection and Memory T Cell Inflation
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CD8 T cell persistence in treated HIV infection
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Carbonylation of the cytoskeletal protein actin leads to aggregate formation
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Cytomegalovirus-Specific T Cell Immunity Is Maintained in Immunosenescent Rhesus Macaques
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Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans
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Varicella Zoster Virus Latency
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Self-citationClinical perspectives on the age-related increase of immunosuppressive activity
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Cellular aging and senescence characteristics of human T-lymphocytes
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Genetics of longevity. Data from the studies on Sicilian centenarians
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Arterial Stiffness Is Associated With Cytomegalovirus‐Specific Senescent CD8 + T Cells
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CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154
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Immune senescence in aged nonhuman primates☆
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Self-citationQuantification of T-cell dynamics during latent cytomegalovirus infection in humans
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Self-citationT-cell ageing in end-stage renal disease patients: Assessment and clinical relevance
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Self-citationAge and CMV-Infection Jointly Affect the EBV-Specific CD8+ T-Cell Repertoire
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Immunology of Aging and Cancer Development
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Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia
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Self-citation
- Authors
- Derhovanessian, E., Larbi, A., & Pawelec, G.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Pawelec, Graham
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 21
- Issue
- 4
- Pages
- 440-445
- ISSN
- 0952-7915 (ISSN-L)
- OpenAlex
- W2061168748
- Cited by
- 220
- References
- 49
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 20 · 2020: 9 · 2019: 13 · 2018: 6 · 2017: 11 · 2016: 16 · 2015: 20 · 2014: 14 · 2013: 19 · 2012: 20
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- immunosenescence, cytomegalovirus infection, biomarkers, betaherpesviruses
- MeSH terms
- Age Factors, Aging, Cytomegalovirus Infections, Cytomegalovirus, Humans, Immune Tolerance, Biomarkers, Age of Onset, Disease Progression
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