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Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses.

  • Rieckmann M Department of Internal Medicine III, University Clinic Halle, Halle, Germany.
  • Delgobo M Department of Internal Medicine I, and.
  • Gaal C Department of Internal Medicine I, and.
  • Büchner L Department of Internal Medicine I, and.
  • Steinau P Department of Internal Medicine III, University Clinic Halle, Halle, Germany.
  • Reshef D Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Gil-Cruz C Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Horst ENT Heart Center, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
  • Kircher M Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
  • Reiter T Department of Internal Medicine I, and.
  • Heinze KG Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
  • Niessen HW Department of Pathology and Cardiac Surgery, Amsterdam UMC, location VUmc, Amsterdam, Netherlands.
  • Krijnen PA Department of Pathology and Cardiac Surgery, Amsterdam UMC, location VUmc, Amsterdam, Netherlands.
  • van der Laan AM Heart Center, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
  • Piek JJ Heart Center, Amsterdam UMC, location AMC, Amsterdam, Netherlands.
  • Koch C Department of Internal Medicine III, University Clinic Halle, Halle, Germany.
  • Wester HJ Pharmaceutical Radiochemistry, Technical University Munich, Munich, Germany.
  • Lapa C Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
  • Bauer WR Department of Internal Medicine I, and.
  • Ludewig B Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Friedman N Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Frantz S Department of Internal Medicine III, University Clinic Halle, Halle, Germany.
  • Hofmann U Department of Internal Medicine III, University Clinic Halle, Halle, Germany.
  • Ramos GC Department of Internal Medicine III, University Clinic Halle, Halle, Germany.
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  • 2019-08-14
Published in:
  • The Journal of clinical investigation. - 2019
Adaptive immunity
Cardiology
Heart failure
Immunology
T cells
Animals
Antigens
Mice
Mice, Transgenic
Myocardial Infarction
Myocardium
Myosin Heavy Chains
Positron Emission Tomography Computed Tomography
T-Lymphocytes, Regulatory
English 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.
Language
  • English
Open access status
green
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Persistent URL
https://sonar.ch/global/documents/621
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