Publication
Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses
Journal Paper/Review - Aug 13, 2019
Rieckmann Max, van der Laan Anja M, Piek Jan J, Koch Charlotte, Wester Hans-Jürgen, Lapa Constantin, Bauer Wolfgang R, Ludewig Burkhard, Friedman Nir, Frantz Stefan, Hofmann Ulrich, Krijnen Paul Aj, Niessen Hans Wm, Delgobo Murilo, Gaal Chiara, Büchner Lotte, Steinau Philipp, Reshef Dan, Gil Cruz Cristina, Ter Horst Ellis N, Kircher Malte, Reiter Theresa, Heinze Katrin G, Ramos Gustavo Campos
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
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.