Introduction: In ST-elevation myocardial infarction (STEMI), inflammation is pivotal, with early senescent CD4+CD28null cells implicated in its pathogenesis. However, the functional phenotype of these cells within the coronary circulation remains unclear. Methods: We examined CD4+ cell subpopulations in blood samples from the coronary sinus and vena cava of 24 STEMI patients and the cephalic vein of seven healthy controls. Results: Our findings revealed reduced CD4+ cell counts in STEMI patients compared to controls (1,998, 1,275–3,268 vs. 4,278, 3,595–4,449), alongside an increased proportion of CD4+ cells lacking CD28 expression (20.1 vs. 6.1%). These CD4+CD28null cells in STEMI predominantly exhibited a Th1 phenotype (47.8% vs. 6.6%). Intriguingly, no significant differences were detected in CD4+CD28null cells between coronary sinus and vena cava, and cytokine levels in these compartments remained similar. Conclusion: CD4+CD28null cells are increased in STEMI, mainly polarized toward a Th1 phenotype, and distributed equally between the different vascular beds.

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