T cells at the heart of cardiac remodelling

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.