**1. Introduction**

Acute MI is the most severe manifestation of coronary artery disease, which causes more than 2.4 million deaths in the USA, more than 4 million deaths in Europe and Northern Asia [1]. During cardiac ischemic events, the heart undergoes deleterious changes that result in cardiac remodeling of the left ventricular (LV) resulting in both structural and functional alternations. The ischemia in the heart triggers an inflammatory response that leads to the formation of a collagen-rich-scar, which is replaced from necrotic tissue to prevent cardiac rupture. Therefore, it is reasonable to conclude that the healing process is tightly coupled with the inflammatory microenvironment of the infarcted heart [2,3].

The cells of the immune system and their secreted factors play crucial roles in the initiation, progression, and resolution of inflammation following MI. Immune cell subsets contribute to both damage and repair of cardiac tissue specifically in regard to scar formation and LV remodeling [4]. Various types of inflammatory cells are recruited to the damaged area in a temporal fashion, where they remove necrotic tissue and promote scar formation [5]. The participation of T cells in myocardial inflammation and repair has been observed in experimental rodent models. In particular, regulatory T cells (Tregs) mainly mediate organ-specific regenerative programs [6–8]. T cell reactivity can benefit myocardial healing by promoting reparative fibrosis in a postmitotic organ [9]. However,

sustained T cell responses in the heart can lead to adverse remodeling and contribute to the progression of ischemic heart failure (HF) at later chronic stages [10]. Temporal and spatial regulation from these biphasic immune cell populations is essential to maintain reparative processes [11]. Importantly, focusing on T cells, including Tregs, can be a clue to reveal the reparative mechanism. Moreover, they can be a target of therapy for patients with ischemic heart disease (IHD).

Pharmacotherapy was traditionally promoted in patients with IHD. After surviving from acute coronary syndrome (ACS), optimal medical therapy (OMT) is a golden standard to prevent cardiovascular death [12]. However, OMT cannot promote a regenerative e ffect in the ischemic area. To date, target therapies are improving and include specific antibodies and the exogenous ubiquitin helping in reducing the scar area in rodent models after cardiac injury [13,14]. In addition, stem cell-based therapies had developed with improvement in cardiac function, however, the overall beneficial e ffects are relatively modest with fundamental mechanisms of stem cell-mediated repair being largely unknown. This review aims to summarize evidence regarding the role of T cell responses in myocardial remodeling following MI, including how stem cell therapies can be used to mediate the ubiquitination state of T cells.
