Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes.
Abstract
Background —Unstable angina (UA) is associated with systemic inflammation and with expansion of interferon-γ–producing T lymphocytes. The cause of T-cell activation and the precise role of activated T cells in plaque instability are not understood. Methods and Results —Peripheral blood T cells from 34 patients with stable angina and 34 patients with UA were compared for the distribution of functional T-cell subsets by flow cytometric analysis. Clonality within the T-cell compartment was identified by T-cell receptor spectrotyping and subsequent sequencing. Tissue-infiltrating T cells were examined in extracts from coronary arteries containing stable or unstable plaque. The subset of CD4 + CD28 null T cells was expanded in patients with UA and infrequent in patients with stable angina (median frequencies: 10.8% versus 1.5%, P <0.001). CD4 + CD28 null T cells included a large monoclonal population, with 59 clonotypes isolated from 20 UA patients. T-cell clonotypes from different UA patients used antigen receptors with similar sequences. T-cell receptor sequences derived from monoclonal T-cell populations were detected in the culprit but not in the nonculprit lesion of a patient with fatal myocardial infarction. Conclusions —UA is associated with the emergence of monoclonal T-cell populations, analogous to monoclonal gammopathy of unknown significance. Shared T-cell receptor sequences in clonotypes of different patients implicate chronic stimulation by a common antigen, for example, persistent infection. The unstable plaque but not the stable plaque is invaded by clonally expanded T cells, suggesting a direct involvement of these lymphocytes in plaque disruption.
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CD28− T cells produce high levels of IFN-γ, have cytotoxic functions, and accumulate in inflammatory lesions.
“CD28− T cells are high producers for interferon-γ (IFN-γ), display cytotoxic functions and accumulate in inflammatory lesions [21–26].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [23]
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- Authors
- Liuzzo, G., Goronzy, J. J., Yang, H., Kopecky, S. L., Holmes, D. R., Frye, R. L., & Weyand, C. M.
- Affiliations
- Mayo Clinic (US)
- From the Department of Medicine, Division of Rheumatology (G.L., J.J.G., H.Y., C.M.W.) and Division of Cardiovascular Diseases (G.L., S.L.K., D.R.H., R.L.F.), Mayo Clinic and Foundation, Rochester, Minn.
- ORCID
- Venue
- Circulation
- Published
- 2000-06-27
- Volume
- 101
- Issue
- 25
- Pages
- 2883-2888
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2058555166
- Cited by
- 552
- References
- 35
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 18 · 2023: 20 · 2022: 14 · 2021: 17 · 2020: 20 · 2019: 17 · 2018: 19 · 2017: 27 · 2016: 23 · 2015: 31 · 2014: 21 · 2013: 32 · 2012: 26
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Mayo Foundation for Medical Education and Research
- National Institutes of Health
- National Eye Institute (R01EY011916, R01 EY 11916)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- unstable angina, acute coronary syndrome, T cell clonality, plaque vulnerability, CD4+CD28- T cells, T cell clonotypes, coronary inflammation, persistent infection, myocardial infarction, stable angina
- MeSH terms
- Acute Disease, Aged, Amino Acid Sequence, Angina, Unstable, Cell Division, Clone Cells, Coronary Vessels, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Receptors, Antigen, T-Cell, T-Lymphocytes, CD4-Positive T-Lymphocytes, CD28 Antigens
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