Gene expression pattern of TCR repertoire and alteration expression of IL-17A gene of γδ T cells in patients with acute myocardial infarction

Abstract

Background: γδ 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.

Methods: 25 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.

Results: The 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.

Conclusions: Restrictive 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.

Keywords: Acute myocardial infarction; Foxp3; IL-17A; γδ T cells.

Fig. 1

Quantitative analysis of mRNA expression levels of TCR Vγ subfamilies genes in γδ T cells of AMI patients and healthy individuals (Control). a Expression levels of TCR Vγ1 genes; b expression levels of TCR Vγ2 genes; c expression levels of TCR Vγ3 genes

Fig. 2

Expression pattern of TCR Vγ subfamilies (TCR Vγ1–3) genes in γδ T cells of AMI patients and healthy individuals (Control)

Fig. 3

Expression clonality of TCR γδ T cells in AMI patients. a The frequencies of TCR γδ repertoire of AMI patients and healthy individuals (Control); b the clonal expansion frequencies of TCR Vγ and Vδ subfamilies of AMI patients and healthy individuals (Control). *P < 0.05

Fig. 4

Subgroup population analysis of Foxp3 and IL-17A genes expression levels in AMI patients and healthy controls. a Comparison of Foxp3 gene expression levels among AMI γδ T cells, AMI PBMCs, normal γδ T cells, and normal PBMCs. b Comparison of IL-17A gene expression levels among AMI γδ T cells, AMI PBMCs, normal γδ T cells, and normal PBMCs