Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation
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CD8+ T cells play a critical role in the immune response to viral pathogens. Persistent human cytomegalovirus (HCMV) infection results in a strong increase in the number of virus-specific, quiescent effector-type CD8+ T cells with constitutive cytolytic activity, but the molecular pathways involved in the induction and maintenance of these cells are unknown. We show here that HCMV infection induced acute and lasting changes in the transcriptomes of virus-reactive T cells collected from HCMV-seropositive patients at distinct stages of infection. Enhanced cell cycle and metabolic activity was restricted to the acute phase of the response, but at all stages, HCMV-specific CD8+ T cells expressed the Th1-associated transcription factors T-bet (TBX21) and eomesodermin (EOMES), in parallel with continuous expression of IFNG mRNA and IFN-γ-regulated genes. The cytolytic proteins granzyme B and perforin as well as the fractalkine-binding chemokine receptor CX3CR1 were found in virus-reactive cells throughout the response. During HCMV latency, virus-specific CD8+ T cells lacked the typical features of exhausted cells found in other chronic infections. Persistent effector cell traits together with the permanent changes in chemokine receptor usage of virus-specific, nonexhausted, long-lived CD8+ T cells may be crucial to maintain lifelong protection from HCMV reactivation.
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Persistent infection with cytomegalovirus and human immunodeficiency virus can induce accumulation of senescent T cells with the described characteristics compared to age-matched seronegative donors.
“Furthermore, persistent infection with viruses including cytomegalovirus (CMV) and human immunodeficiency virus (HIV) can induce the accumulation of senescent T cells with all the characteristics described above, compared to age matched seronegative donors [34, 39, 40].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [40]
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Senescence of T Lymphocytes: Implications for Enhancing Human Immunity
Akbar, A. N., Henson, S. M., & Lanna, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.09.002 · Cited by 285 · see citing works
New advances in CMV and immunosenescence
Sansoni, P., Vescovini, R., Fagnoni, F. F., Akbar, A., Arens, R., Chiu, Y.-L., Čičin-Šain, L., Dechanet-Merville, J., Derhovanessian, E., Ferrando-Martinez, S., et al. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.020 · Cited by 150 · see citing works
Self-citationArmed and Ready: Transcriptional Regulation of Tissue-Resident Memory CD8 T Cells
Behr, F. M., Chuwonpad, A., Stark, R., & van Gisbergen, K. P. J. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01770 · Cited by 124 · see citing works
Blimp‐1 induces and Hobit maintains the cytotoxic mediator granzyme B in CD8 T cells
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Self-citation
- Authors
- Hertoghs, K. M. L., Moerland, P. D., van Stijn, A., Remmerswaal, E. B. M., Yong, S. L., van de Berg, P. J. E. J., van Ham, S. M., Baas, F., ten Berge, I. J. M., & van Lier, R. A. W.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Amsterdam Neuroscience (NL)
- Venue
- Journal of Clinical Investigation
- Published
- 2010-11-01
- Volume
- 120
- Issue
- 11
- Pages
- 4077-4090
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2964975
- OpenAlex
- W2161071827
- Cited by
- 198
- References
- 83
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 9 · 2022: 5 · 2021: 15 · 2020: 14 · 2019: 10 · 2018: 16 · 2017: 7 · 2016: 21 · 2015: 16 · 2014: 14 · 2013: 6 · 2012: 22
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Nierstichting (C03.2034, C05.2141)
- Norwegian Biodiversity Information Centre
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Keywords
- human cytomegalovirus, CD8+ T cells, T cell differentiation, viral persistence, T-bet, Eomesodermin, interferon-gamma, granzyme B, perforin, CX3CR1, T cell exhaustion, viral latency, HCMV reactivation, transcriptome, effector memory T cells
- MeSH terms
- Cell Differentiation, Cell Separation, Cytomegalovirus Infections, Cytomegalovirus, Flow Cytometry, Humans, Lymphocyte Activation, Biomarkers, Virus Latency, CD8-Positive T-Lymphocytes, Gene Expression Profiling, Microarray Analysis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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