Age-Associated Increase of Low-Avidity Cytomegalovirus-Specific CD8+ T Cells That Re-Express CD45RA
Open accessAbstract
The mechanisms regulating memory CD8+ T cell function and homeostasis during aging are unclear. CD8+ effector memory T cells that re-express CD45RA increase considerably in older humans and both aging and persistent CMV infection are independent factors in this process. We used MHC class I tetrameric complexes that were mutated in the CD8 binding domain to identify CMV-specific CD8+ T cells with high Ag-binding avidity. In individuals who were HLA-A*0201, CD8+ T cells that expressed CD45RA and were specific for the pp65 protein (NLVPMVATV epitope) had lower avidity than those that expressed CD45RO and demonstrated decreased cytokine secretion and cytolytic potential after specific activation. Furthermore, low avidity NLVPMVATV-specific CD8+ T cells were significantly increased in older individuals. The stimulation of blood leukocytes with CMV lysate induced high levels of IFN-α that in turn induced IL-15 production. Moreover, the addition of IL-15 to CD45RA−CD45RO+ CMV-specific CD8+ T cells induced CD45RA expression while Ag activated cells remained CD45RO+. This raises the possibility that non-specific cytokine–driven accumulation of CMV-specific CD8+CD45RA+ T cells with lower Ag-binding avidity may exacerbate the effects of viral reactivation on skewing the T cell repertoire in CMV-infected individuals during aging.
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CMV-specific CD8+ effector memory cells reexpressing CD45RA typically have low avidity and appear to expand mainly in response to antigen-nonspecific cytokine stimulation.
“A recent study exploring the avidity of CMV-specific CD8+ T cells has demonstrated that CD8+ effector memory cells reexpressing CD45RA typically have low avidity and appear to expand mostly in response to antigen-nonspecific cytokine stimulation [32].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [32]
The narrowing of the TCR repertoire may be associated with an age-associated increase in the proportion of low-avidity virus-specific CD8+ T cells, as shown in CMV infection.
“This may be associated with an age-associated increase in the proportion of low-avidity virus-specific CD8+ T cells, as shown in the case of CMV infection for instance [89].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [89]
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- Authors
- Griffiths, S. J., Riddell, N. E., Masters, J., Libri, V., Henson, S. M., Wertheimer, A., Wallace, D., Sims, S., Rivino, L., Larbi, A., Kemeny, D. M., Nikolich-Zugich, J., Kern, F., Klenerman, P., Emery, V. C., & Akbar, A. N.
- Affiliations
- University College London (GB)
- Division of Infection and Immunity, University College London , London WC1E 6BT,
- University of Arizona (US)
- National Institute for Health and Care Research (GB)
- National University of Singapore (SG)
- Agency for Science, Technology and Research (SG)
- Department of Immunobiology, Arizona Center on Aging, University of Arizona College of Medicine , Tucson, AZ 85724
- Brighton and Sussex Medical School (GB)
- Department of Cellular and Microbial Sciences, University of Surrey , Surrey GU2 7XH,
- Corresponding author
- Masters, Joanne
- Libri, Valentina
- Wallace, Diana
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-06-01
- Volume
- 190
- Issue
- 11
- Pages
- 5363-5372
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3736312
- OpenAlex
- W2153331359
- Cited by
- 82
- References
- 54
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 13 · 2013: 6
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- National University of Singapore (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Wellcome Trust (061100, 091663)
- National Institute for Health and Care Research (NF-SI-0510-10204)
- Biotechnology and Biological Sciences Research Council (BBS/B/04528, BB/E019188/1, BB/H020519/1)
- National Institute on Aging (R01AG035309)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- cytomegalovirus, CD8+ T cells, CD45RA, CD45RO, aging, IL-15, interferon-alpha, viral reactivation, HLA-A*0201, cytotoxicity
- MeSH terms
- Age Factors, Antibody Affinity, Antigens, Cytomegalovirus Infections, Cytomegalovirus, Dendritic Cells, Humans, Lymphocyte Activation, Monocytes, Phosphoproteins, Viral Matrix Proteins, HLA-A2 Antigen, Immunophenotyping, Interferon-alpha, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Interleukin-15
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