Abstract
Background: Activated inflammatory cells are found in coronary plaques as well as peripheral circulation in patients with acute coronary syndrome. We explored the circulating T cell profile, their reactivity to self-antigens and plasma cytokine levels in Indian patients with Myocardial Infarction. Methods and Results: Intracellular expression of interferon-γ Interleukin (IL)-4, IL-17, IL-10 and Foxp3 were determined in CD4+ and CD8+ T cells using flow cytometry in patients with ST elevated myocardial infarction (STEMI) (N = 79) and controls (N = 80). Cytokines were measured using Milliplex kit and T cell reactivity was studied by CFSE dilution. Statistical analysis was performed using SPSS software. Patients with myocardial infarction showed higher proportion of IL-17 expressing CD4+ and CD8+ T cells (Th17 and Tc17) and elevated levels of IL-6 and IL-17 in plasma with significant reduction in circulating Tregs. Th1, Th2 and CD4+CD28null cells were not significantly different in patients compared to healthy individuals. The ratio of Th17 and Tc17 to Tregs showed an independent association with STEMI with an adjusted odds ratio of 2.92 (95% CI: 1.73 - 4.92), P < 0.001 and 2.22 (95% CI: 1.42 - 3.44), P < 0.001 respectively. Reactivity to HSP60 and oxidized LDL with expansion of IL-17 expression was higher in patients compared with control. Young patients (<45 years) with no apparent risk factor could be distinguished from healthy controls by the increase in Th17 and ratio of Th17 and Tc17 to Tregs in peripheral blood. Conclusion: Our results suggest that an imbalance in both CD4+ and CD8+ T cells secreting IL-17 and Tregs is associated with acute myocardial infarction. HSP60 and Ox-LDL may contribute to this response and pathogenesis of AMI in Indian population.
Highlights
Coronary artery disease (CAD) is the most significant cause of global mortality despite advances in medicine and drug development [1]
HSP60 and oxidized LDL (Ox-LDL) may contribute to this response and pathogenesis of AMI in Indian population
We investigated the independent contributions of specific T cell subsets including the CD4+ and CD8+ T lymphocytes with intracellular expression of interferon γ (IFN-γ), IL-17, IL-4 and Treg to myocardial infarction, and correlated serum cytokine levels and antigen reactivity to the T cells in an attempt to understand the role of specific T lymphocytes in atherosclerosis and atherothrombosis
Summary
Coronary artery disease (CAD) is the most significant cause of global mortality despite advances in medicine and drug development [1]. Regulatory T cells (Tregs) are known to suppress the inflammatory response and have a protective role in atherosclerosis [8]. We explored the circulating T cell profile, their reactivity to self-antigens and plasma cytokine levels in Indian patients with Myocardial Infarction. Methods and Results: Intracellular expression of interferon-γ Interleukin (IL)-4, IL-17, IL-10 and Foxp were determined in CD4+ and CD8+ T cells using flow cytometry in patients with ST elevated myocardial infarction (STEMI) (N = 79) and controls (N = 80). Patients with myocardial infarction showed higher proportion of IL-17 expressing CD4+ and CD8+ T cells (Th17 and Tc17) and elevated levels of IL-6 and IL-17 in plasma with significant reduction in circulating Tregs. Young patients (
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