Recurrent Adrenergic Stress Provokes Persistent Myocarditis in PD-1–Deficient Mice

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.