CD8 T‐cells regulate macrophage recruitment leading to exacerbated cardiac remodeling

Abstract

Elevated CD8 T‐cell counts (>1065 cells/mm3) have been linked with increased mortality rate (2‐fold) in patients after myocardial infarction (MI). However, the exact mechanisms by which CD8 T‐cells impair cardiac wound healing post‐MI are not totally understood. We hypothesized that CD8 T‐cells regulate the inflammatory response leading to decreased survival and cardiac function post‐MI. Permanent occlusion of the left anterior descending artery was performed on C57BL/6J (WT; 4.5±0.1 months of age; n=6 males and females/day) and CD8atm1Mak mice (CD8KO; 4.1±0.2 months of age; n=6 males and females/day). CD8KO mice had improved day 7 survival (73%) compared to WT mice (50%; p<0.05). Interestingly, 100% of the CD8KO mice who died did so due to cardiac rupture of the left ventricle (LV; rupture/total deaths; 3/3) whereas 50% of WT animals (5/10; p<0.05) died of cardiac rupture. Strain analysis showed that as early as post‐MI day 3, global longitudinal strain was improved in CD8KO animals (−5.3±0.1%) compared to WT (−2.8±0.1%; p<0.05) suggesting WT mice have increased myocardial wall stress. Echocardiography measured at day 7 post‐MI showed improved cardiac physiology, as indicated by fractional shortening in CD8KO mice (11±2%) compared to WT mice (5±1%; p<0.05) implicating CD8 T‐cells as a negative regulator of wound healing during the later phase post‐MI. Proteomic plasma analysis of 111 proteins indicated CD8KO had elevated immune response at both post‐MI day 3 and day 7. This was supported by increased macrophage numbers at day 3 post‐MI in CD8KO animals compared to WT mice (p<0.05) as shown by Mac3 staining of the infarct. Collagen within the infarct was also elevated at day 3 in CD8KO compared to WT (p<0.05) as shown by picosirius red staining implicating CD8 T‐cells in regulation of myocardial fibrosis. In conclusion, CD8 T‐cells regulate macrophage recruitment and impair collagen deposition during the early phase post‐MI leading to adverse cardiac remodeling and decreased survival.Support or Funding InformationThis work was supported by the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award IK2BX003922 to KYD‐P. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Veterans Administration.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.