418 CD8+ T-cell transfer induces adverse alterations to the post-myocardial infarction scar

Objectives/Goals: Cardiovascular disease, particularly myocardial infarction (MI), is a leading cause of death in the USA. Previous studies have identified CD8+ T-cells as adverse regulators post-MI. We hypothesized that CD8+ T-cells impair cardiac function by altering scar composition. Methods/Study Population: MI was induced by permanent ligation of the coronary artery in C57BL6/J (WT; 3–7 mo) and CD8atm1mak mice (CD8-/-; 3–7 mo). CD8-/- mice were injected with either vehicle or naïve splenic CD8+ T-cells (2x10^6 cells/injection) via tail vein, 4 hours after ligation. Tissue was collected at Day 7 post-MI for biomechanical testing and further downstream analyses. Granzyme (Gzm)A, B, and K were tested for collagen cleavage using a fluorogenic cleavage assay. Effect on collagen production in TGF-β-activated cardiac fibroblasts was assessed in vitro by stimulating cells with GzmA, B, and K (25 AU) for 24 hours. Results/Anticipated Results: CD8-/- mice had improved ejection fraction and LV dilation at Day 7 post-MI compared to WT and CD8-/- mice resupplemented with splenic CD8+ T-cells (p Discussion/Significance of Impact: Our study demonstrates that CD8+ T-cells regulate cardiac fibrosis partially through Gzm release, resulting in left ventricular biomechanical impairments and increased dilation.