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We hypothesized that CD8<jats:sup>+<\/jats:sup>T-cells regulate the inflammatory response, leading to decreased survival and cardiac function post-MI. We performed permanent occlusion of the left anterior descending coronary artery on C57BL\/6J and CD8a<jats:sup>tm1mak<\/jats:sup>mice (deficient in functional CD8<jats:sup>+<\/jats:sup>T-cells). CD8a<jats:sup>tm1mak<\/jats:sup>mice had increased survival at 7 days post-MI compared with that of the wild-type (WT) and improved cardiac physiology at day 7 post-MI. Despite having less mortality, 100% of the CD8a<jats:sup>tm1mak<\/jats:sup>group died because of cardiac rupture compared with only 33% of the WT. Picrosirius red staining and collagen immunoblotting indicated an acceleration of fibrosis in the infarct area as well as remote area in the CD8a<jats:sup>tm1mak<\/jats:sup>mice; however, this increase was due to elevated soluble collagen implicating poor scar formation. Plasma and tissue inflammation were exacerbated as indicated by higher levels of Cxcl1, Ccl11, matrix metalloproteinase (MMP)-2, and MMP-9. Immunohistochemistry and flow cytometry indicated that the CD8a<jats:sup>tm1mak<\/jats:sup>group had augmented numbers of neutrophils and macrophages at post-MI day 3 and increased mast cell markers at post-MI day 7. Cleavage of tyrosine-protein kinase MER was increased in the CD8a<jats:sup>tm1mak<\/jats:sup>mice, resulting in delayed removal of necrotic tissue. In conclusion, despite having improved cardiac physiology and overall survival, CD8a<jats:sup>tm1mak<\/jats:sup>mice had increased innate inflammation and poor scar formation, leading to higher incidence of cardiac rupture. Our data suggest that the role of CD8<jats:sup>+<\/jats:sup>T-cells in post-MI recovery may be both beneficial and detrimental to cardiac remodeling and is mediated via a cell-specific mechanism.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY We identified new mechanisms implicating CD8<jats:sup>+<\/jats:sup>T-cells as regulators of the post-myocardial infarction (MI) wound healing process. Mice without functional CD8<jats:sup>+<\/jats:sup>T-cells had improved cardiac physiology and less mortality 7 days post MI compared with wild-type animals. Despite having better overall survival, animals lacking functional CD8<jats:sup>+<\/jats:sup>T-cells had delayed removal of necrotic tissue, leading to poor scar formation and increased cardiac rupture, suggesting that CD8<jats:sup>+<\/jats:sup>T-cells play a dual role in the cardiac remodeling process.<\/jats:p>","DOI":"10.1152\/ajpheart.00112.2019","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T14:35:33Z","timestamp":1563546933000},"page":"H581-H596","source":"Crossref","is-referenced-by-count":96,"title":["CD8<sup>+<\/sup>T-cells negatively regulate inflammation post-myocardial infarction"],"prefix":"10.1152","volume":"317","author":[{"given":"Daria V.","family":"Ilatovskaya","sequence":"first","affiliation":[{"name":"Division of Nephrology, Departments of Medicine and Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cooper","family":"Pitts","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Clayton","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Domondon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Departments of Medicine and Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Pippin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-6112","authenticated-orcid":false,"given":"Kristine Y.","family":"DeLeon-Pennell","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina"},{"name":"Research Service, Ralph H. 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