Martín, PilarSánchez-Madrid, Francisco2025-06-172025-06-172025-01-16J Clin Invest. 2025 Jan 16;135(2):e185218.https://hdl.handle.net/20.500.12105/26760Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with inflammation playing a pivotal role in its pathogenesis. T lymphocytes are crucial components of the adaptive immune system that have emerged as key mediators in both cardiac health and the development and progression of CVD. This Review explores the diverse roles of T cell subsets, including Th1, Th17, γδ T cells, and Tregs, in myocardial inflammatory processes such as autoimmune myocarditis and myocardial infarction. We discuss the contribution of T cells to myocardial injury and remodeling, with emphasis on specific immune receptors, e.g., CD69, that have a critical role in regulating immune tolerance and maintaining the balance between T cell subsets in the heart. Additionally, we offer a perspective on recent advances in T cell-targeted therapies and their potential to modulate immune responses and improve clinical outcomes in patients with CVD and in heart transplant recipients. Understanding the intricate interplay between T cells and cardiovascular pathology is essential for developing novel immunotherapeutic strategies against CVD.This study was supported by grants from the Madrid Regional Government (S2022/BMD-7209-INTEGRAMUNE-CM) to PM and FSM. PM’s laboratory is funded by MCIN-ISCIII-Fondo de Investigación Sanitaria (PI22/01759), cofunded by the European Regional Development Fund (ERDF), and by PMPTA22/00090-BIOCARDIOTOX, cofunded by NextGEN, as well as the Fundació La Marató TV3 (grant 202325 30 31). FSM’s laboratory is funded by the Spanish Ministry of Science and Innovation, Agencia Estatal de Investigación grant PID2023- 149541OB-I00, “La Caixa” Foundation project code LCF/PR/HR23/52430018, and a grant from the Asociación Española Contra el Cáncer (AECC; PRYCO223002PEIN). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).engVoRhttp://creativecommons.org/licenses/by/4.0/Attribution 4.0 International39817455Journal of Clinical Investigationopen access