Author(s)

Thiruvelselvan Ponnusamy¹, Komarlu Venkatachala Srikanth², Ramanjappa Manjunatha³, Vijay V. Kakkar^4,5, Lakshmi Mundkur^4*

¹Research Scholar, Manipal University at Thrombosis Research Institute, Bangalore, India.
²Narayana Institute of Cardiac Sciences, Bangalore, India.
³Clinical Research Unit, Thrombosis Research Institute, Bangalore, India.
⁴Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India.
⁵Molecular Immunology Unit, Thrombosis Research Institute, London, United Kingdom.

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⁺CD28^null 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.

T Lymphocytes, Adaptive Immunity, Coronary Artery Disease, Myocardial Infarction, Cytokines, Auto-Antigens

Ponnusamy, T. , Srikanth, K. , Manjunatha, R. , Kakkar, V. and Mundkur, L. (2015) Circulating Th17 and Tc17 Cells and Their Imbalance with Regulatory T Cells Is Associated with Myocardial Infarction in Young Indian Patients. World Journal of Cardiovascular Diseases, 5, 373-387. doi: 10.4236/wjcd.2015.512043.