Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes.
BACKGROUND
Unstable angina (UA) is associated with systemic inflammation and with expansion of interferon-gamma-producing T lymphocytes. The cause of T-cell activation and the precise role of activated T cells in plaque instability are not understood.


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.
Liuzzo
G
G
Department of Medicine, Division of Rheumatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Goronzy
J J
JJ
Yang
H
H
Kopecky
S L
SL
Holmes
D R
DR
Frye
R L
RL
Weyand
C M
CM
D000208:Acute Disease; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D000789:Angina, Unstable / Q000235:genetics / Q000473:pathology*; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002999:Clone Cells; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology* / Q000502:physiology
D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell