Abstract
It is unclear how the immune system initiates effective tissue repair responses without also simultaneously activating adaptive immune responses to self-antigens released by damaged or necrotic cells. We studied the role of repetitive adrenergic mediated stress on cardiac injury wild-type and programmed death-1-deficient (PD-1(-/-)) mice treated with 3 intraperitoneal low doses of isoproterenol followed by an intraperitoneal injection of high-dose ISO 7 days later (ISO(primed)/ISO(injury)). Repetitive adrenergic stress in ISO(primed)/ISO(injury) PD-1(-/-) mice resulted in a persistent dysregulated myocardial inflammatory response characterized by the expansion of autoreactive effector CD8(+) T cells, increased cardiac hypertrophy, mild left ventricular dysfunction, and increased lethality when compared with ISO(primed)/ISO(injury) wild-type mice.