Monoclonal T-Cell Proliferation and Plaque Instability in Acute Coronary Syndromes
- 27 June 2000
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 101 (25), 2883-2888
- https://doi.org/10.1161/01.cir.101.25.2883
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+CD28nullT cells was expanded in patients with UA and infrequent in patients with stable angina (median frequencies: 10.8% versus 1.5%,P+CD28nullT 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.Keywords
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