(Circulation. 2000;101:2883.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Monoclonal T-Cell Proliferation and Plaque Instability in Acute Coronary Syndromes
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.
Correspondence to C.M. Weyand, MD, PhD, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905. E-mail weyand.cornelia{at}mayo.edu
Background—Unstable angina (UA)
is associated with systemic inflammation and with expansion of
interferon-
–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+CD28null 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+CD28null 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.
Key Words: angina • plaque • lymphocytes • cytokines • immune system
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