BACKGROUND AND PURPOSE - Evidence is accumulating that infection with influenza A virus contributes to atherothrombotic disease. Vaccination against influenza decreases the risk of atherosclerotic syndromes, indicating that inflammatory mechanisms may be involved. We tested the hypothesis that influenza A virus-specific T cells contribute to atherosclerotic plaque inflammation, which mediates the onset of plaque rupture. METHODS - T-cell cultures were generated from atherosclerotic segments and peripheral blood of 30 patients with symptomatic carotid artery disease. The response of plaque and peripheral blood T cells to influenza A virus was analyzed and expressed as a stimulation index (SI). Selective outgrowth of intraplaque influenza A-specific T cells was calculated by the ratio of plaque T cell SI and peripheral blood T cell SI for each patient. Accordingly, the patients were categorized as high- (SI ratio ≥5), intermediate- (5 <SI ratio ≤2), and non- (SI ratio <2) responders. The presence of influenza A virus in the vessel fragments was evaluated by reverse transcription-polymerase chain reaction. RESULTS - High proliferative responses of plaque-derived T cells to influenza A virus were frequently observed. Among the 30 patients, 5 were categorized as high responders, 10 were intermediate responders, and 15 were nonresponders. Live influenza A virus could not be detected in the atherosclerotic plaques by polymerase chain reaction. CONCLUSIONS - Selective outgrowth of influenza A virus-specific T cells occurs within the microenvironment of human atherosclerotic plaques. Influenza virus-derived antigens or alternatively, mimicry antigens, appear to be potential candidates for triggering or sustaining plaque inflammation, which eventually leads to symptomatic plaque complications.

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Keywords Atherosclerosis, Carotid artery, Infectious disease, Influenza, T lymphocytes
Persistent URL dx.doi.org/10.1161/STROKEAHA.107.491282, hdl.handle.net/1765/28811
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Citation
Keller, T.T., van der Meer, J.J., Teeling, P., van der Sluijs, K.F., Idu, M.M., Rimmelzwaan, G.F., … de Boer, O.J.. (2008). Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques. Stroke, 39(1), 174–179. doi:10.1161/STROKEAHA.107.491282