The roles of Th cells in myocardial infarction

Abstract

Myocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue damage. A significant aspect of this condition is reperfusion injury, which occurs when blood flow is restored but exacerbates the damage. This review first addresses the role of the innate immune system, including neutrophils and macrophages, in the cascade of events leading to myocardial infarction and reperfusion injury. It then shifts focus to the critical involvement of CD4+ T helper cells in these processes. These cells, pivotal in regulating the immune response and tissue recovery, include various subpopulations such as Th1, Th2, Th9, Th17, and Th22, each playing a unique role in the pathophysiology of myocardial infarction and reperfusion injury. These subpopulations contribute to the injury process through diverse mechanisms, with cytokines such as IFN-γ and IL-4 influencing the balance between tissue repair and injury exacerbation. Understanding the interplay between the innate immune system and CD4+ T helper cells, along with their cytokines, is crucial for developing targeted therapies to mitigate myocardial infarction and reperfusion injury, ultimately improving outcomes for cardiac patients.

Fig. 1. Overview of the lymphoid and myeloid cells’ role after reperfusion of myocardial infarction is depicted in this figure.

It illustrates the pro-inflammatory and subsequent anti-inflammatory phases of repair and remodeling after reperfusion in myocardial infarction. The accumulation of multiple cells, including neutrophils, monocytes, macrophages, NK cells, dendritic cells, B lymphocytes, and CD8+ T cells, infiltrate the infarct zone. These cells exert pro-inflammatory, anti-inflammatory, or differential effects on fibrosis and pro-angiogenesis.

Fig. 2. A schematic representation of the process of T-cell development.

The diagram illustrates the differentiation of T cells from HSCs into distinct subtypes of Th cells. The development of Th cells begins with HSCs in the bone marrow, differentiating into CLPs. These CLPs migrate to the thymus, undergoing selection to become mature CD4+ T cells. The mature CD4+ T cells then travel to peripheral lymphoid organs (e.g., lymph nodes and spleen), where they are activated by antigens presented by APCs. This activation involves interactions between MHC class II and co-stimulatory molecules on APCs with TCR and CD28 on T cells, leading to their differentiation into various Th cell subtypes based on environmental signals.

Fig. 3. General overview of the role of CD4+ T helper cell subsets after reperfusion in myocardial infarction.

The figure demonstrates the responses of Th1, Th2, Th9, Th17, and Th22 cells to reperfusion after myocardial infarction. This includes their direct effects on the infarcted myocardium or indirect effects on post-infarction myocardial tissues through interactions with other leukocytes. The figure also shows the mutual influences and interactions of the subsets in MI and reperfusion injury.