Selective Expansion of Influenza A Virus–Specific T Cells in Symptomatic Human Carotid Artery Atherosclerotic Plaques

Abstract

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 Ն5), intermediate-(5 ϽSI ratio Յ2), and non-(SI ratio Ͻ2) 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

Activation of T Lymphocytes in Atherosclerotic Plaques

“…One possible explanation of the fact that CD8 rather than CD4 T cells seem to be activated is that the antigens that activate T cells may be of viral or endogenous nature (e.g. a heat shock protein or oxydated forms of LDL 3, 11, 23, 24 . In the future, our approach may allow the expansion of T cells in order to test this speculation.…”

Translational Mini-Review Series on Immunology of Vascular Disease: Inflammation, infections and Toll-like receptors in cardiovascular disease

“…This revealed increased numbers of macrophages in the adventitia, more T lymphocytes in the adventitia and periadventitial fat and more dendritic cells in the intima and media of those patients who had suffered an infection [65]. T lymphocytes isolated from atherosclerotic plaques were more responsive to influenza A virus than those purified from peripheral blood of the same donor, suggesting a mechanism of influenza-induced plaque inflammation [66].…”

Design and rationale for the I nfluenza vaccination A fter M yocardial I nfarction (IAMI) trial. A registry-based randomized clinical trial

“…The FLUVACS study randomized 301 patients (200 with AMI and 101 for whom percutaneous coronary intervention (PCI) was scheduled) to either influenza vaccine or a control group (8 The pathophysiological background for a putative benefit of influenza vaccination in ACS may comprise protective effects from inflammation, anticoagulant effects and prevention of increased metabolic demand with infection. It is conceivable that influenza increase cytokine production leading to plaque destabilization (12) plaque rupture (13) and triggering of the coagulation cascade (14). B-cells may play a role in atherogenesis (15) and the humoral response following an influenza vaccination stimulus involves multiple B cell subsets generating a multifaceted humoral response that provides protective antibodies (16) which might contribute to the possible protection against ACS.…”

“…Because influenza may precipitate plaque rupture(13) it is possible that a single influenza vaccination in the early phase after an AMI may stabilize nonculprit coronary plaques(25). End points beyond 1 year will be regarded as exploratory.…”