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Thromb Haemost 2025; 125(07): 697-712
DOI: 10.1055/a-2437-6111
Atherosclerosis and Ischaemic Disease

Characterization of CD3+ T Lymphocytes in Human Coronary Thrombi with ST-segment Elevation Myocardial Infarction

Muyang Gu   *
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Ni Xia   *
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Si Zhang
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Xinyu Zhu
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Meilin Liu
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Yuzhi Lu
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Nana Li
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Haoyi Yang
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Tingting Tang
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Shaofang Nie
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Jingyong Li
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Fen Yang
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Jiao Jiao
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Bingjie Lv
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Weimin Wang
4   Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Desheng Hu
5   Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Jiong Hu
6   Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Huirong Liu
7   Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
,
Chen Chen
8   Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
,
Xiang Cheng
1   Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2   Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3   Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
› Author Affiliations
Funding This work was supported by grants from the National Natural Science Foundation of China [No. 82030016 and 82230011 to X.C.; No. 82200320 to M.G.; No. 82170282 to N.X.; No. 82000443 to J.L.].
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Abstract

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.

Keyword

STEMI - T lymphocyte - coronary thrombosis - platelets - T cell receptors

Authors' Contribution

M.G., N.X., and X.C. designed the study. M.G., N.X., Y.L., S.N., and J.J. enrolled participants and supervised study participant recruitment. M.G., X.Z., M.L., N.L., and H.Y. collected the samples and performed the experiments. M.G., S.Z., and T.T. designed and performed the analysis. M.G. and N.X. prepared the manuscript and the figures. N.X., X.C., J.L., F.Y., B.L., H.L., and C.C. edited and revised the manuscript. X.C., W.W., D.H., and J.H. supervised the project. All the authors contributed to the interpretation of the results and the composition of the final manuscript. All the authors have read and approved the final version of the paper.


* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 28 February 2024

Accepted: 09 October 2024

Article published online:
07 November 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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