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

Tomohiro Hayashi, Kenji Rowel Q. Lim, Attila Kovacs, Douglas L. Mann

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish
Pages (from-to)1503-1517
Number of pages15
JournalJACC: Basic to Translational Science
Issue number12
StatePublished - Dec 2023


  • immune checkpoints
  • inflammation
  • myocarditis
  • tissue injury


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