Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques.
OBJECTIVE
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 >or=5), intermediate- (5 <SI ratio <or=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.
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Tymen T
TT
Keller
Jelger J
JJ
van der Meer
Peter
P
Teeling
Koen
K
van der Sluijs
Mirza M
MM
Idu
Guus F
GF
Rimmelzwaan
Marcel
M
Levi
Allard C
AC
van der Wal
Onno J
OJ
de Boer
D000956:Antigens, Viral / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000276:immunology* / Q000473:pathology; D016893:Carotid Stenosis / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D016894:Endarterectomy, Carotid; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications
D000956:Antigens, Viral