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- Title
Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses.
- Authors
Rieckmann, Max; Delgobo, Murilo; Gaal, Chiara; Büchner, Lotte; Steinau, Philipp; Reshef, Dan; Gil-Cruz, Cristina; ter Horst, Ellis N.; Kircher, Malte; Reiter, Theresa; Heinze, Katrin G.; Niessen, Hans W. M.; Krijnen, Paul A. J.; van der Laan, Anja M.; Piek, Jan J.; Koch, Charlotte; Wester, Hans-Jürgen; Lapa, Constantin; Bauer, Wolfgang R.; Ludewig, Burkhard
- 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.
- Subjects
T helper cells; MYOCARDIAL infarction; T cells; GENE expression profiling; SUPPRESSOR cells
- Publication
Journal of Clinical Investigation, 2019, Vol 129, Issue 11, p4922
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI123859