Cardiac CD8 T Cells Exhibit Temporal Differences in Heterogeneity Post-MI

Over 800,000 people in the U.S. have a myocardial infarction (MI) each year. Following an MI, the body mounts an inflammatory and wound healing process to develop a scar in place of the dead and injured cardiomyocytes. CD8+ T-cells are known to be present in the left ventricle (LV), and we have previously shown that they are adverse regulators of MI remodeling. Further, we have found that CD8+ T-cells experience shifts in both numbers and phenotypes during the acute post-MI wound healing process. We hypothesized that CD8+ T-cells at isolated at various time points post-MI would exhibit temporal shifts in heterogeneity in phenotypic markers, including expression of cytokines, chemokines, and granzymes. To test this hypothesis, we induced MI by permanent ligation of the left anterior descending coronary artery in male and female C57Bl6J mice (n ≥ 3 mice per sex) and collected at days 1, 3, 7, and 14 post-MI. Echocardiography was performed at baseline and before terminal collection to assess cardiac function and confirm injury. Each LV was dissociated and T-cells were isolated using flow sorting. T-cells were then fixed, barcoded, and underwent single-cell RNA sequencing. CD8+ T-cells were identified and differences in heterogeneity were observed across the four time points, with those isolated at day 3 post-MI exhibiting the most diversity and cells from day 7 post-MI exhibiting the least. At day 3 post-MI, CD8+ T-cells expressed markers including Ly6c2, Ccl3, Ccl5, Gzma, and Gzmb, among others. At day 7 post-MI, CD8+ T-cells mainly showed high expression of Gzma. CD8+ T-cells isolated at days 1 and 14 showed similar diversity, expressing genes including Gzma and Il1b. Interestingly, females exhibited more phenotypic heterogeneity than males at every time point besides day 7. This project has the potential to identify phenotypic changes in CD8+ T-cells in during the various stages of post-MI healing, exposing cellular mechanisms that govern their role as negative regulators of LV remodeling. Results from this study will inform future immunotherapies targeting CD8+ T-cells after myocardial injury. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.