Abstract
Backgroundγδ T cells are associated with the pathogenesis of coronary atherosclerotic heart disease, but the relationship between the development of acute myocardial infarction (AMI) and γδ T cells is not clear. So we attempt to investigate the expression pattern and clonality of T cell receptor (TCR) repertoire of γδ T cells in AMI patients, analyze the expression levels of regulatory genes Foxp3 and IL-17A, and characterize the correlation between γδ T cells and the pathogenesis of AMI.Methods25 patients diagnosed with ST-segment-elevation AMI were enrolled and 14 healthy individuals were recruited as the controls. RT-PCR and GeneScan were used to analyze the complementarity-determining region 3 sizes of TCR γδ repertoire genes in sorted γδ T cells from peripheral blood mononuclear cells (PBMCs). RQ-PCR was used to detect the gene expression levels of Foxp3, IL-17A and TCR Vγ subfamilies in sorted γδ T cells. All the patients were followed up for recordings of clinical endpoints.ResultsThe mRNA gene expression levels of TCR Vγ1, Vγ2, and Vγ3 subfamilies in AMI patients were significantly higher than those in healthy controls. The expression pattern was Vγ1 > Vγ2 > Vγ3 in AMI patients, while Vγ1 > Vγ3 > Vγ2 in healthy controls. The significantly restricted expression of TCR Vδ subfamilies were also found in AMI patients. The expression frequencies of TCR Vδ7 and TCR Vδ6 in AMI patients were significantly lower than those in healthy controls. The high clonal expansion frequencies of the TCR Vδ8, Vδ4 and Vδ3 were determined in AMI patients. High expression of Foxp3 gene was found in AMI PBMCs, while high expression of IL-17A was found in AMI γδ+ cells.ConclusionsRestrictive expression of TCR γδ repertoire and alteration expression of IL-17A gene are the important characteristics of γδ T cells in AMI patients, which might be related to the immune response and clinical outcome. γδ T cells might play a key role in the pathological progress of AMI and associated with the IL-17A mediated pathway.
Highlights
The early and effective primary percutaneous coronary intervention and thrombolytic therapy have greatly improved the survival and cardiac function in patients with acute myocardial infarction (AMI), AMI is still a major cause of morbidity and mortality throughout the world, accounting for 7 and 5% of the global burden of disease in males and females, respectively [1]
During the follow-up, one patient died of ventricular septal perforation, one of the AMI complications; and another patient died of cerebral hemorrhage 2 months after AMI
As for the source of IL-17 in clinical AMI, we found high expression of IL-17A in γδ T cells in AMI, which is consistent with a few literatures, further clinical studies in larger sample of AMI patients and animal experiment researches are needed
Summary
The early and effective primary percutaneous coronary intervention and thrombolytic therapy have greatly improved the survival and cardiac function in patients with acute myocardial infarction (AMI), AMI is still a major cause of morbidity and mortality throughout the world, accounting for 7 and 5% of the global burden of disease in males and females, respectively [1]. JUPITER studies have showed that even those healthy participants without traditional risk factors, but with increased high-sensitive-C reactive protein (hsCRP), benefited from statin in therapy [2]. Studies have showed that innate and acquired immune markers such as hsCRP were associated with the progression of atherosclerosis [4, 5], which indicated that both innate and adaptive immunity contributed to the development of the atherosclerosis and its complications [6]. Innate inflammatory mediators were found to be up-regulated during and after AMI, suggesting that myocardial infarction (MI) mobilizes a sterile nonspecific inflammation, and ‘adaptive’ immune responses to cardiac auto-antigens which are able to modulate the myocardial inflammation and fibrosis [5, 7]
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