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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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“…has included insights into the role of inflammatory mediators in cardiovascular disease, and characterization of immunologic phenomena that are present in coronary vascular disease but may also be found in classic autoimmune diseases [Mustafa et al. 2000; Liuzzo et al. 1999; Cristea et al. 1986].”
Background
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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