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-J. rgen Wester, Constantin Lapa, Wolfgang R. Bauer, Burkhard LudewigNir Friedman, Stefan Frantz, Ulrich Hofmann, Gustavo Campos Ramos

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, 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 α (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in Balb/c mice. Transferred MYHCA 614–629-specific CD4+ T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lymph nodes (med-LNs) of infarcted mice, acquired a Treg phenotype with a distinct prohealing gene expression profile, and mediated cardioprotection. Myocardial Tregs were also detected in autopsy samples from patients who had had a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in patients with MI. 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 that MI context induces prohealing T cell autoimmunity in mice and confirm the existence of an analogous heart/med-LN/T cell axis in patients with MI.

Original languageEnglish
Pages (from-to)4922-4936
Number of pages15
JournalJournal of Clinical Investigation
Volume129
Issue number11
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

Rieckmann, M., Delgobo, M., Gaal, C., Büchner, L., Steinau, P., Reshef, D., ... Ramos, G. C. (2019). Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses. Journal of Clinical Investigation, 129(11), 4922-4936. https://doi.org/10.1172/JCI123859