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Characterization of CD3+ T Lymphocytes in Human Coronary Thrombi with ST-segment Elevation Myocardial Infarction
Muyang Gu1,2,3, Ni Xia1,2,3, Si Zhang1,2,3
1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
This study reveals increased T cell clonality in ST-segment elevation myocardial infarction (STEMI) coronary thrombi, suggesting specific immune responses drive atherothrombosis and offering new therapeutic targets.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Genomics
Background:
- ST-segment elevation myocardial infarction (STEMI) involves coronary atherothrombosis, where immune responses play a key role.
- The exact causes of atherothrombosis and the specific T cell-mediated immune responses in STEMI coronary thrombi remain unclear.
Purpose of the Study:
- To investigate the heterogeneity and clonality of CD3+ T lymphocytes within STEMI coronary thrombi and peripheral blood at a single-cell level.
Main Methods:
- Single-cell RNA and T cell receptor (TCR) sequencing were employed.
- Analysis included CD3+ T lymphocytes from STEMI coronary thrombi, peripheral blood of STEMI patients, and blood from non-coronary artery disease (CAD) controls.
Main Results:
- CD3+ T lymphocytes in STEMI coronary thrombi showed reduced activation, cytotoxicity, and pro-inflammatory/pro-thrombotic characteristics compared to peripheral blood.
- Increased CD3+ T cell clonality was observed in coronary thrombi.
- T lymphocytes from STEMI patients displayed upregulated genes linked to recent TCR engagement, indicating antigen-specific stimulation and potential shared antigen targets across patients.
Conclusions:
- This research elucidates the cellular heterogeneity of CD3+ T lymphocytes in STEMI.
- Understanding the adaptive immune mechanisms in atherothrombosis can pave the way for targeted therapies against aberrant immune responses for improved STEMI treatment.
Background:
The occurrence and development of ST-segment elevation myocardial infarction (STEMI) are accompanied by coronary atherothrombosis and occlusion, and immune responses play prominent roles in their pathogeneses. However, the causes of atherothrombosis remain elusive, and a comprehensive study of T cell-mediated immune responses in coronary thrombi from STEMI patients is lacking.
Objectives:
The aim of this study was to determine the heterogeneity and clonality of CD3+ T lymphocytes in STEMI patients at the single-cell level.
Methods:
Paired single-cell RNA and T cell receptor (TCR) sequencing was performed on CD3+ T lymphocytes in the coronary thrombi and peripheral blood of STEMI patients, as well as the blood from control subjects without coronary artery disease (CAD).
Results:
Compared with those in the peripheral blood of STEMI patients, the activation, cytotoxicity, proinflammatory, and prothrombotic characteristics of CD3+ T lymphocytes in coronary thrombi were decreased, and the clonality of CD3+ T cells was increased. Compared with those from non-CAD controls, T lymphocytes from STEMI patients exhibited an upregulation of genes related to recent TCR engagement, suggesting antigen-specific stimulation in STEMI. Antigen specificity prediction using an algorithm indicated the probability of T cells from different patients binding to similar antigens for clonal expansion during STEMI.
Conclusion:
This study provides a basis for exploring the cellular heterogeneity of CD3+ T lymphocytes in the coronary thrombi and peripheral blood of STEMI patients. Identifying the precise adaptive immune mechanisms driving atherothrombosis may lead to innovative therapies that selectively target the aberrant immune response, resulting in more effective treatments for STEMI.
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