TY - JOUR
T1 - Selective expansion of influenza a virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques
AU - Keller, Tymen T.
AU - van der Meer, Jelger J.
AU - Teeling, Peter
AU - van der Sluijs, Koen
AU - Idu, Mirza M.
AU - Rimmelzwaan, Guus F.
AU - Levi, Marcel
AU - van der Wal, Allard C.
AU - de Boer, Onno J.
PY - 2008
Y1 - 2008
N2 - 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
AB - 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
U2 - https://doi.org/10.1161/STROKEAHA.107.491282
DO - https://doi.org/10.1161/STROKEAHA.107.491282
M3 - Article
C2 - 18048854
SN - 0039-2499
VL - 39
SP - 174
EP - 179
JO - Stroke; a journal of cerebral circulation
JF - Stroke; a journal of cerebral circulation
IS - 1
ER -