J. Clin. Invest. 129, 4922–4936 (2019)

Myocardial infarction (MI) — the leading cause of death in the developed world — has a well-described pathological contribution from inflammation and the innate immune system; however, whether or not adaptive immunity has a predominantly harmful or reparative role is less clear. In The Journal of Clinical Investigation, Ramos and colleagues use a cardiac epitope screen in a mouse model of MI to find autoreactive T cells specific for peptides derived from the heart protein MYHCA. Far from being pathogenic, these MYHCA-autoreactive T cells assume a regulatory T cell phenotype, express genes encoding wound-healing molecules and exert a cardioprotective effect. Necropsies of patients who suffered an MI also show an increase in cells expressing the regulatory T cell transcription factor Foxp3. Heart-autoreactive T cells might therefore serve an important role in ameliorating MI — at least in the acute phase of the disease.