Regulatory Role of CD4+ T Cells in Myocarditis

Abstract EN

Myocarditis is an important cause of heart failure in young patients.

Autoreactive, most often, infection-triggered CD4+ T cells were confirmed to be critical for myocarditis induction.

Due to a defect in clonal deletion of heart-reactive CD4+ T cells in the thymus of mice and humans, significant numbers of heart-specific autoreactive CD4+ T cells circulate in the blood.

Normally, regulatory T cells maintain peripheral tolerance and prevent spontaneous myocarditis development.

In the presence of tissue damage and innate immune activation, however, activated self-antigen-loaded dendritic cells promote CD4+ effector T cell expansion and myocarditis.

So far, a direct pathogenic role has been described for both activated Th17 and Th1 effector CD4+ T cell subsets, though Th1 effector T cell-derived interferon-gamma was shown to limit myocarditis severity and prevent transition to inflammatory dilated cardiomyopathy.

Interestingly, recent observations point out that various CD4+ T cell subsets demonstrate high plasticity in maintaining immune homeostasis and modulating disease phenotypes in myocarditis.

These subsets include Th1 and Th17 effector cells and regulatory T cells, despite the fact that there are still sparse and controversial data on the specific role of FOXP3-expressing Treg in myocarditis.

Understanding the specific roles of these T cell populations at different stages of the disease progression might provide a key for the development of successful therapeutic strategies.