Massive Load of Functional Effector CD4+ and CD8+ T Cells against Cytomegalovirus in Very Old Subjects
Open accessAbstract
A progressive, systemic, and low-grade proinflammatory status is one of the major characteristics of immunosenescence. Emerging data suggest a possible contribution of CMV, known to chronically infect a large proportion of humans, lifelong from newborns to centenarians. To test this hypothesis, we evaluated functional T cell responses to two CMV immunogenic proteins, pp65 and IE-1, in 65 chronically infected subjects aged 25–100 years. PBMC were stimulated with mixtures of peptides spanning the entire sequence of both proteins, and Ag specificity and magnitude of intracellular IFN-γ- and TNF-α-positive cells were then analyzed within both CD4+ and CD8+ T cells. Results indicate that pp65 and, to a lesser extent, IE-1 constitute major Ags against which aged people target functionally efficient T cell effector responses with massive production of Th1 cytokines and exhibition of CD107a degranulation marker. As a result, the production of IFN-γ induced in T cells by both Ags was seven to eight times greater in very old than in young subjects. The comparative analysis of pp65-specific responses in these very long-term carriers revealed a reciprocal relationship between CD4+ and CD8+ producing IFN-γ in the same individuals. These results indicate that CMV represents an important pathogen responsible for a strong immune activation in human aging. Such a remarkable burden of effector CD4+ and CD8+ T cells may be necessary to protect the elderly from CMV endogenous reactivation, but can turn detrimental by giving a substantial contribution to the proinflammatory status that accompanies the main age-related diseases.
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Human CMV-specific memory T cells can comprise up to 50% of the total memory T cell compartment in older individuals.
“This situation might explain why the human CMV-specific memory T cells can comprise up to 50% of the total memory T cell compartment in older individuals123,124 and leads to the hypothesis that persistent human CMV infection has a role in immunosenescence and inflammageing.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [123]
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Self-citation
- Authors
- Vescovini, R., Biasini, C., Fagnoni, F. F., Telera, A. R., Zanlari, L., Pedrazzoni, M., Bucci, L., Monti, D., Medici, M. C., Chezzi, C., Franceschi, C., & Sansoni, P.
- Affiliations
- University of Parma (IT)
- Istituti Clinici Scientifici Maugeri (IT)
- University of Florence (IT)
- University of Bologna (IT)
- Corresponding author
- Vescovini, Rosanna
- Biasini, Claudia
- Zanlari, Luca
- Pedrazzoni, Mario
- Sansoni, Paolo
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-09
- Volume
- 179
- Issue
- 6
- Pages
- 4283-4291
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1553612782
- Cited by
- 173
- References
- 49
- Citations by year
- 2026: 7 · 2025: 1 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 18 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 10 · 2013: 16 · 2012: 11
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Regione Emilia-Romagna
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Keywords
- cytomegalovirus, immunosenescence, pp65, IE1, CD4+ T cells, CD8+ T cells, T cell effector responses, interferon-gamma, TNF-α, CD107a degranulation, Th1 cytokines, chronic viral infection, aging, proinflammation, cytomegalovirus reactivation, age-related diseases
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cytomegalovirus, Cytotoxicity Tests, Immunologic, Humans, Interferon-gamma, Lymphocyte Activation, Peptides, Phosphoproteins, Tumor Necrosis Factor-alpha, Viral Matrix Proteins, Viral Proteins, CD4-Positive T-Lymphocytes, Immediate-Early Proteins, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte
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