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Perturbation of the T-cell repertoire in patients with unstable angina.
Abstract
Background —Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-γ is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald’s class IIIB) and with stable angina (SA). Methods and Results —Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4 + and CD8 + T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA was associated with an increased number of CD4 + and CD8 + T cells producing IFN-γ, whereas patients with SA had higher frequencies of IL-2 + and IL-4 + CD4 + T cells. Expansion of the IFN-γ + T-cell population in UA persisted for at least 3 months. Increased production of IFN-γ in UA could be attributed to the expansion of an unusual subset of T cells, CD4 + CD28 null T cells. Conclusions —Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-γ production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-γ is produced by CD4 + CD28 null T cells, which are expanded in UA and distinctly low in SA and controls. The emergence of CD4 + CD28 null T cells may result from persistent antigenic stimulation.
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“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 [24]
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“Specifically, patients with unstable angina have an overrepresentation of T cells (CD4 ) with an increase in intracellular IFN-γ levels.(9) These results suggest that the involvement of the immune responses influence the progression of coronary arteriosclerosis.”
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BackgroundNK Cells Contribute to the Immune Risk Profile in Kidney Transplant Candidates
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“CD4+/28CD–/CD57+ senescent T cells, which are associated with unstable atherosclerotic plaques (63, 64) and clinical coronary atherosclerosis (17, 18, 65–67) are seen essentially only in IRP+ patients.”
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“It has been reported that the Th1 cells were predominant in ACS(67,68) and unstable angina pectoris (UA).(69,70) Similarly, a Th17/Tregs imbalance has been associated with plaque destabilization and its progression.”
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“These cells have a distinctive T cell phenotype and have gained cytolytic activity through expression of perforin and granzymeB, which can damage vascular endothelial cells [63] and release large amounts of IFN+ [62], a potent stimulus of macrophages.”
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“1989), that does not express the co-estimulatory receptor CD28 (CD4+CD28null) (Liuzzo et al. 1999) (Zal et al.”
BackgroundT helper cell related interleukins and the angiographic morphology in unstable angina
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Metadata
- Authors
- Liuzzo, G., Kopecky, S. L., Frye, R. L., Fallon, W. M. O., Maseri, A., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- From the Departments of Medicine (G.L., S.L.K., R.L.F., J.J.G., C.M.W.) and Biostatistics (W.M.O.), Mayo Clinic, Rochester, Minn; and the Division of Cardiology (A.M.), Catholic University, Rome, Italy.
- Venue
- Circulation
- Published
- 1999-11-23
- Volume
- 100
- Issue
- 21
- Pages
- 2135-2139
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1976292294
- Cited by
- 398
- References
- 17
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 12 · 2023: 8 · 2022: 12 · 2021: 9 · 2020: 12 · 2019: 13 · 2018: 10 · 2017: 18 · 2016: 17 · 2015: 17 · 2014: 14 · 2013: 16 · 2012: 21
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- unstable angina, stable angina, T cell receptor repertoire, interferon-gamma, CD4+CD28- T cells, CD8+ T cells, CD4+ T cells, cytokine production, monocyte activation, acute phase response, interleukin-6, interleukin-2, IL-4
- MeSH terms
- Adult, Aged, Angina, Unstable, Female, Humans, Interferon-gamma, Male, Middle Aged, Monocytes, T-Lymphocytes, CD4 Antigens, CD28 Antigens
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