Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Cardiovascular Medicine, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, China.
J Transl Med. 2019 Feb 6;17(1):40. doi: 10.1186/s12967-019-1788-4.
Acute myocardial infarction (AMI) is characterized by an inflammatory process in which T cell plays a key role. However, the profile of immune microenvironment in AMI is still uncertain. High-throughput sequencing of T cell receptor (TCR) provides deep insight into monitoring the immune microenvironment.
30 patients with AMI were enrolled and 30 healthy individuals were recruited as controls. Flow cytometer were used to analyze the distribution of αβ T cells and their CD69 expression from peripheral leukomonocytes. TCRβ repertoire library was amplified by two-round multiplex PCR and detected by next-generation sequencing (NGS).
The percentage of αβ T cells in AMI patients were significantly restricted than those in healthy controls, while the highly activated αβ T cells along with distinguishing usage of variable (V), diversity (D) and joining (J) gene segments were also found in AMI patients. In addition, AMI induced a significantly restricted CDR3 amino acid (AA) diversity and remarkably reconstituted TCR immune repertoires. Finally, we identified several AMI-associated tendency of CDR3 AAs expression after AMI.
Our work suggests that the aberrant αβ T cells distribution and activation may associated with the pathogenesis of AMI and demonstrates a reconstitution of TCRβ immune repertoire after AMI.
急性心肌梗死(AMI)的特征是炎症过程,其中 T 细胞发挥关键作用。然而,AMI 中的免疫微环境特征仍不确定。T 细胞受体(TCR)的高通量测序提供了监测免疫微环境的深入见解。
纳入 30 例 AMI 患者和 30 例健康个体作为对照。使用流式细胞仪分析外周白细胞中αβ T 细胞及其 CD69 表达的分布。通过两轮多重 PCR 扩增 TCRβ 库,并通过下一代测序(NGS)进行检测。
AMI 患者的αβ T 细胞百分比明显受限,而高度活化的αβ T 细胞以及区分使用可变(V)、多样性(D)和连接(J)基因片段也在 AMI 患者中发现。此外,AMI 诱导明显受限的 CDR3 氨基酸(AA)多样性,并显著重建 TCR 免疫库。最后,我们确定了 AMI 后 CDR3 AA 表达的几个与 AMI 相关的趋势。
我们的工作表明,异常的αβ T 细胞分布和激活可能与 AMI 的发病机制有关,并表明 AMI 后 TCRβ 免疫库的重建。