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 (ISOprimed/ISOinjury). Repetitive adrenergic stress in ISOprimed/ISOinjury 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 ISOprimed/ISOinjury wild-type mice. (J Am Coll Cardiol Basic Trans Science 2023;8:1503-1517) Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).