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.
Keller
Tymen T
TT
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
van der Meer
Jelger J
JJ
Teeling
Peter
P
van der Sluijs
Koen
K
Idu
Mirza M
MM
Rimmelzwaan
Guus F
GF
Levi
Marcel
M
van der Wal
Allard C
AC
de Boer
Onno J
OJ
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