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Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling.

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Lemarié, Jeremie 
Zlatanova, Ivana 
Cachanado, Marine 
Seghezzi, Jean-Christophe 


Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction.



Animals, Apoptosis, CD8-Positive T-Lymphocytes, Disease Models, Animal, Female, Granzymes, Heart, Heart Failure, Homeodomain Proteins, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardial Infarction, Myocardium, Swine, Transcriptome, Ventricular Remodeling

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Nat Commun

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Springer Science and Business Media LLC


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British Heart Foundation (CH/10/001/27642)
British Heart Foundation (CH/10/001/27642)
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