In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

T cells at the heart of cardiac remodelling

Basic Science - Cardiac Diseases - Leukocytes, Inflammation, Immunity
Cardiac Diseases


Innate immunity and inflammation have been recognised to partake in heart failure progression since decades. Clinical trials investigating anti-inflammatory therapies for heart failure, however, have failed so far1. Adaptive immunity has been less scrutinised, mostly because appropriate tools to decipher cell-specific responses such as genetic models, cardiac flow cytometry protocols, or sequencing approaches have been developed later. The effect of lymphocytes, with more data being available on T than B cells, differs according to injury and subtype studied2.
Here, Pilar Alcaide and co-workers now add another piece to the puzzle and provide compelling evidence for heart specific T cell driven immune responses that promote heart failure progression. The authors demonstrate that cardiac T cell antigen recognition increases in pressure overloaded mouse hearts and this was linked to a restricted T cell receptor repertoire. Major histocompatibility complex (MHC) II presentation of endogenous cardiac antigens to CD4+ T cells was required to develop dysfunction after pressure overload. Further, reactive oxygen species (ROS) associated isolevuglandin (IsoLG)-modified cardiac proteins appear to act as neo-antigens thus linking ROS, potentially derived from myeloid cells or resident cell mitochondrial ROS, to T cell mediated immunity and cardiac remodelling. IsoLG scavenging with 2-hydroxybenzylamine (2-HOBA) mitigated these responses and ameliorated cardiac dysfunction supporting this hypothesis.
Together, these data suggest that heart-specific T cell responses are key modulators of cardiac remodelling and heart failure. Importantly, T cell responses may also foster cardiac repair after injury, such as in the case of regulatory T cells upon myocardial infarction3. Thus, a precise understanding of the injury and time-dependent dynamic interplay of different immune cell subtypes is necessary to develop therapeutic approaches in the context of immunity related cardiac remodelling. The current study adds another piece towards this understanding.

References


1. Adamo L, Rocha-Resende C, Prabhu SD, Mann DL. Reappraising the role of inflammation in heart failure. Nat Rev Cardiol. 2020 May;17(5):269-285. doi: 10.1038/s41569-019-0315-x. Epub 2020 Jan 22. PMID: 31969688.

2. Ramos G, Hofmann U, Frantz S. Immune repertoires in the failing heart: the global picture. Eur Heart J. 2019 Dec 21;40(48):3934-3936. doi: 10.1093/eurheartj/ehz548. PMID: 31390007.

3. 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, Ramos GC. Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses. J Clin Invest. 2019 Aug 13;129(11):4922-4936. doi: 10.1172/JCI123859. PMID: 31408441; PMCID: PMC6819128.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.