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Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses

Max Rieckmann, Murilo Delgobo, Chiara Gaal, Lotte Büchner, Philipp Steinau, Dan Reshef, Cristina Gil Cruz, Ellis N Ter Horst, Malte Kircher, Theresa Reiter, Katrin G Heinze, Hans Wm Niessen, Paul Aj Krijnen, Anja M Van Der Laan, Jan J Piek, Charlotte Koch, Hans-Jürgen Wester, Constantin Lapa, Wolfgang R Bauer, Burkhard Ludewig, Nir Friedman, Stefan Frantz, Ulrich Hofmann & Gustavo Campos Ramos

abstract 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.
   
citation Rieckmann M, Delgobo M, Gaal C, Büchner L, Steinau P, Reshef D, Gil Cruz C, Ter Horst E N, Kircher M, Reiter T, Heinze K G, Niessen H W, Krijnen P A, van der Laan A M, Piek J J, Koch C, Wester H J, Lapa C, Bauer W R, Ludewig B, Friedman N, Frantz S, Hofmann U, Ramos G C. Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses. J Clin Invest 2019; 130:.
   
type journal paper/review (English)
date of publishing 13-08-2019
journal title J Clin Invest (130)
ISSN electronic 1558-8238
PubMed 31408441
DOI 10.1172/JCI123859