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

[摘要] 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. 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.

[关键词] C-REACTIVE PROTEIN;UNSTABLE ANGINA;RHEUMATOID-ARTHRITIS;MYOCARDIAL-INFARCTION;ARTERY DISEASE;ATHEROSCLEROSIS;RUPTURE;ACTIVATION;REPERTOIRE;EXPRESSION