Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes

Giovanna Liuzzo, Jörg J. Goronzy, Hongyu Yang, Stephen L. Kopecky, David Holmes, Robert L. Frye, Cornelia M. Weyand

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413 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2883-2888
Number of pages6
JournalCirculation
Volume101
Issue number25
DOIs
StatePublished - Jun 27 2000

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Keywords

  • Angina
  • Cytokines
  • Immune system
  • Lymphocytes
  • Plaque

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Liuzzo, G., Goronzy, J. J., Yang, H., Kopecky, S. L., Holmes, D., Frye, R. L., & Weyand, C. M. (2000). Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation, 101(25), 2883-2888. https://doi.org/10.1161/01.CIR.101.25.2883