Heart-specific T cell responses: from antigens to disease mechanisms

The field of immunology has transformed our understanding of myocardial cell biology and paved the way for new pathophysiological concepts in cardiology. Researchers have sought to elucidate the contributions of nonspecific inflammatory mechanisms to cardiac diseases, and an increasing number of clinical trials have explored anti-inflammatory approaches in cardiovascular disease. Moreover, adaptive immune mechanisms directed to cardiac proteins released by dying cardiomyocytes have been reported across a broad spectrum of conditions, including acute myocarditis, myocardial infarction and heart failure, and have gained increasing attention. This concept of antigen-specific cardio-immune crosstalk could pave the way for a deeper understanding of tissue-specific disease mechanisms and facilitate the development of targeted interventions. However, only a small number of cardiac antigens have been identified so far, and an immunological definition of heart specificity remains elusive. This Review revisits the molecular composition of the heart from the perspective of T cells to describe the most relevant cardiac antigens identified to date, thus defining a framework for identifying novel T cell reactivities in the injured heart. Going forward, these insights might pave the way for the development of new tools to track specific T cells across various cardiac diseases, in contexts ranging from model organisms to patients.