Abstract MP263: CD8+ T-cells Regulate Macrophage Recruitment And Retention After Myocardial Infarction

Heart failure is the number one reason for admission, with myocardial infarctions (MI) as the underlying etiology in of 70% cases. Macrophages facilitate cardiac healing after the MI. Resident macrophages die due to the initial ischemic event and are replaced by monocyte-derived macrophages. The adaptive immune system, including cytotoxic CD8+ T-cells, are known regulators of inflammation and are upregulated in the circulation and in the infarct after an MI. Previously we showed mice deficient in CD8+ T-cells were protected from adverse remodeling. We hypothesized that after an MI, CD8+ T-cells regulate the recruitment and retention of monocytes. To test our hypothesis, C57Bl6J (WT; n≥3/day post-MI) and mice deficient in CD8+ T-cells (CD8-/-; n≥3/day post-MI) underwent permanent occlusion and tissue was collected at post-MI days 0 (no MI), 1, 3, 7, and 14. Mac3 staining of the infarct was performed to determine the macrophage time course. Infarct tissue was analyzed by bulk RNAseq (n=3/day/genotype) to determine possible genetic regulators at post-MI days 1, 7, and 14. Data was clustered based on the genetic markers of macrophage subtypes identified in previous single cell genomic studies. Mac3 staining of WT mice showed macrophages begin to infiltrate as early as post-MI day 1, peaking at day 7, and beginning to reach baseline levels by day 14. Interestingly, CD8-/- mice had a delay in macrophage recruitment at day 1; however, by day 3 there was almost double the amount of macrophages compared to the WT group. While no differences were observed at day 7 post-MI, CD8-/- mice had elevated macrophages at post-MI day 14 compared to the WT mice. Based on the gene clusters, the infarct tissue of CD8-/- mice had increased markers of resident-like macrophages at post-MI days 7 and 14 compared to WT mice. Resident macrophages have been shown to be cardioprotective post-MI, suggesting a possible protective mechanism in CD8-/- mice. In conclusion, our data indicates that CD8+ T-cells influence cardiac remodeling over the post-MI time course by facilitating in macrophage recruitment and retention. Furthermore, in the absence of CD8+ T-cells, there was an increase in resident-like macrophages that could prove to point to a more favorable repopulation of cells post-MI.