1. Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses.
- Author
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Rieckmann M, Delgobo M, Gaal C, Büchner L, Steinau P, Reshef D, Gil-Cruz C, Horst ENT, Kircher M, Reiter T, Heinze KG, Niessen HW, Krijnen PA, van der Laan AM, Piek JJ, Koch C, Wester HJ, Lapa C, Bauer WR, Ludewig B, Friedman N, Frantz S, Hofmann U, and Ramos GC
- Subjects
- Animals, Antigens genetics, Mice, Mice, Transgenic, Myocardial Infarction diagnostic imaging, Myocardial Infarction genetics, Myocardial Infarction pathology, Myocardium pathology, Myosin Heavy Chains genetics, Positron Emission Tomography Computed Tomography, T-Lymphocytes, Regulatory pathology, Antigens immunology, Myocardial Infarction immunology, Myocardium immunology, Myosin Heavy Chains immunology, T-Lymphocytes, Regulatory immunology
- 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.
- Published
- 2019
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