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Broadly targeted human cytomegalovirus-specific CD4 + and CD8 + T cells dominate the memory compartments of exposed subjects
Open accessAbstract
Human cytomegalovirus (HCMV) infections of immunocompetent hosts are characterized by a dynamic, life-long interaction in which host immune responses, particularly of T cells, restrain viral replication and prevent disease but do not eliminate the virus or preclude transmission. Because HCMV is among the largest and most complex of known viruses, the T cell resources committed to maintaining this balance have never been characterized completely. Here, using cytokine flow cytometry and 13,687 overlapping 15mer peptides comprising 213 HCMV open reading frames (ORFs), we found that 151 HCMV ORFs were immunogenic for CD4+ and/or CD8+ T cells, and that ORF immunogenicity was influenced only modestly by ORF expression kinetics and function. We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average ∼10% of both the CD4+ and CD8+ memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8+ T cells and was rare. These data provide the first glimpse of the total human T cell response to a complex infectious agent and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.
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“Infection with CMV causes a large accumulation of virus-specific memory T cells, so that approximately 10 % of the CD4+ and CD8+ T cell pool becomes specific for this virus (Sylwester et al. 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Sylwester et al. 2005
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“It is therefore currently unknown whether values such as 10 % of the CD4+ and CD8+ T cell pool being specific for CMV is above, or below, the ideal threshold (Sylwester et al. 2005).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Sylwester et al. 2005
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Cites
Duration of antiviral immunity after smallpox vaccination
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“Significantly, of the 62 ORFs that failed to generate a response in our seropositive subjects, 26 were on a list of 34 ORFs that newer annotation approaches indicate have low coding potential and therefore are unlikely to represent bona fide HCMV ORFs (27).”
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Kotton, C. N., Kumar, D., Caliendo, A. M., Åsberg, A., Chou, S., Snydman, D. R., Allen, U., & Humar, A. (2010) · Transplantation · doi:10.1097/tp.0b013e3181cee42f · Cited by 1,560
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Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences
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“As an example, the lifelong need to control CMV seems to cause a broad shift in the magnitude and complexity of many cell subsets (Chidrawar et al., 2009; Wills et al., 2011), and 10% of all T cells in CMV+ individuals can be directed against this virus (Sylwester et al., 2005).”
BackgroundInfluentialThe “Silent” Global Burden of Congenital Cytomegalovirus
Manicklal, S., Emery, V. C., Lazzarotto, T., Boppana, S. B., & Gupta, R. K. (2013) · Clinical Microbiology Reviews · doi:10.1128/cmr.00062-12 · Cited by 1,030
“immune system (181), major targets include the pp65 tegument”
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“In a separate study, Sylwester et al. (2005) found that approximately 10% of CD4+ and CD8+ memory T cells in CMV seropositive subjects can be directed against the virus.”
Background
Metadata
- Authors
- Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., Nelson, J. A., & Picker, L. J.
- Affiliations
- Oregon National Primate Research Center (US)
- Corixa Corporation (US)
- Stiftung Charité (DE)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-09-05
- Volume
- 202
- Issue
- 5
- Pages
- 673-685
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2212883
- OpenAlex
- W2103849595
- Cited by
- 1,339
- References
- 41
- Citations by year
- 2026: 39 · 2025: 53 · 2024: 56 · 2023: 41 · 2022: 56 · 2021: 70 · 2020: 67 · 2019: 81 · 2018: 71 · 2017: 86 · 2016: 74 · 2015: 77 · 2014: 56 · 2013: 83 · 2012: 64
- FWCI
- 38.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RR 00163, AI21640)
- National Institute of Allergy and Infectious Diseases (R01AI047606, AI 47606, R01AI021640)
- National Center for Research Resources (P51RR000163, M01RR000334)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- human cytomegalovirus, CD4+ T cells, CD8+ T cells, immunodominance, seropositive individuals, viral persistence
- MeSH terms
- Adult, Cytomegalovirus Infections, Cytomegalovirus, Female, Flow Cytometry, Humans, Immunogenetics, Immunologic Memory, Male, Middle Aged, Peptides, Serologic Tests, CD4-Positive T-Lymphocytes, Open Reading Frames, CD8-Positive T-Lymphocytes
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