Publication

Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses

Journal Paper/Review - Aug 13, 2019

Units
PubMed
Doi

Citation
Rieckmann M, van der Laan A, Piek J, Koch C, Wester H, Lapa C, Bauer W, Ludewig B, Friedman N, Frantz S, Hofmann U, Krijnen P, Niessen H, Delgobo M, Gaal C, Büchner L, Steinau P, Reshef D, Gil Cruz C, Ter Horst E, Kircher M, Reiter T, Heinze K, Ramos G. Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses. J Clin Invest 2019; 130
Type
Journal Paper/Review (English)
Journal
J Clin Invest 2019; 130
Publication Date
Aug 13, 2019
Issn Electronic
1558-8238
Brief description/objective

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Herein, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class-II-restricted epitopes, we found that myosin heavy chain alpha (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in mice. Transferred MYHCA614-629-specific CD4+ T (TCR-M) cells selectively accumulated in the myocardium and mediastinal lymph nodes (med-LN) of infarcted mice, acquired a Treg phenotype with a distinct pro-healing gene expression profile, and mediated cardioprotection. Myocardial Treg cells were also detected in autopsies from patients who suffered a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in MI-patients. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence showing that MI-context induces pro-healing T cell autoimmunity in mice and confirms the existence of an analogous heart/med-LN/T cell axis in MI patients.