Epstein–Barr virus-specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential
Open accessAbstract
During acute infection, latent and lytic Epstein-Barr virus (EBV) epitope-specific CD8+ T cells have a CD45RO+CD45RA− phenotype. However, after resolution of the infection, a large proportion of these cells, particularly those specific for lytic viral epitopes, re-express the CD45RA molecule. The role of CD8+ CD45RA+ T cells in ongoing immunity to EBV and other viruses is unknown. We now demonstrate that, relative to their CD45RO+ counterparts, the EBV-specific CD8+ T cells that revert to CD45RA expression after acute infectious mononucleosis are not in cell cycle, have longer telomeres, and are more resistant to apoptosis partly because of increased Bcl-2 expression. However, the EBV-specific CD8+CD45RA+ T cells have shorter telomeres than the total CD8+ CD45RA+ T-cell pool and predominantly express low levels of the CCR7 chemokine receptor, indicating that they are not naive cells. In addition, EBV-specific CD8+CD45RA+ T cells can be induced to proliferate and exhibit potent cytotoxic activity against target cells loaded with specific peptide. Our results strongly suggest, therefore, that EBV-specific CD8+ CD45RA+ T cells represent a stabilized virus-specific memory pool and not terminally differentiated effector cells. The identification of mechanisms that enable stable virus-specific CD8+ T cells to persist after acute infection may lead to the enhancement of antiviral immunity in immunocompromised and elderly persons.
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Compared to less differentiated populations, senescent T cells secrete high levels of inflammatory cytokines IFN-gamma and TNF-alpha after short term activation.
“In comparison to less differentiated populations, senescent T cells also secrete high levels of inflammatory cytokines such IFN and TNF after short term activation [28, 30, 50]”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [50]
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- Authors
- Dunne, P. J., Faint, J. M., Gudgeon, N. H., Fletcher, J. M., Plunkett, F. J., Soares, M. V. D., Hislop, A. D., Annels, N. E., Rickinson, A. B., Salmon, M., & Akbar, A. N.
- Affiliations
- From the Department of Clinical Immunology, Royal Free and University College Medical School, London; the Cancer Research Campaign Institute for Cancer Studies, Birmingham University Medical School; and the Medical Research Council Centre for Immune Regulation, Birmingham University Medical School, United Kingdom.
- The Royal Free Hospital (GB)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2002-08-01
- Volume
- 100
- Issue
- 3
- Pages
- 933-940
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2095616499
- Cited by
- 144
- References
- 41
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 6 · 2012: 7
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- European Commission
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- Epstein-Barr virus, CD8+ T cells, memory T cells, apoptosis resistance, Bcl-2, telomere length, CCR7, cytotoxic T lymphocytes, infectious mononucleosis, antiviral immunity, T cell proliferation
- MeSH terms
- Acute Disease, Cell Division, Herpesvirus 4, Human, Humans, Immunologic Memory, Infectious Mononucleosis, Telomere, Apoptosis, Leukocyte Common Antigens, Antigen Presentation, CD8-Positive T-Lymphocytes
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