Lymphocytic subsets play distinct roles in heart diseases

Figures

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  Figure 1. B-cells response to heart injury in experimental and clinical studies. B-cells infiltrate into the myocardium after myocardial damage. Proteins and cytokines released from necrotic cardiomyocytes recognized by circular and cardiac infiltrated B-cells, causing B-cells activation. Then the activated B-cells induce direct cardiac injury via complement-mediated cytotoxicity and apoptotic signaling pathway (A). While, some activated circular B-cells transform into plasma and memory B-cells that produce autoantibodies. The recognition of autoantibodies and cardiomyocytes further cause deterioration of heart function. These include apoptosis of cardiomyocytes, increased collagen deposition, the release of pro-inflammatory cytokines, and rational hypertrophy (B). Meanwhile, activated B-cells, with the participation of Th1 cells, regulate the recruitment of Ly-6Chigh monocytes from the blood into injured myocardium through a CCL-7 dependent fashion. The supplement of cardiac monocytes aggravates the damage to heart function (C).

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  Figure 2. Role of T-cells in experimental models of heart injury. T-cells infiltrate into the myocardium after myocardial injury. The infiltrated γδT cells in injured myocardium promote the production of IL-17A, which mediate the apoptosis of cardiomyocytes by regulating the ratio of Bax/Bcl-2. Conventional T (Tconv) cells in damaged myocardium promote myocardium injury, induce proinflammatory monocyte recruitment and a proinflammatory milieu. IFN-γ that produced by T cells, aggravates cardiac injury and apoptosis of cardiomyocytes. Tregs promote anti-inflammatory milieu through inhibit the accumulation of inflammatory cells (such as neutrophils, monocytes and Tconv cells) and the production of inflammatory cytokines (TNF-α, IL-1β, IFN-γ, etc.). In addition, Tregs inhibit the M1-macrophages differentiation from Ly-6Chigh monocytes and derived cytokines (IL-10, IL-13, TGFβ) induce an M2-like differentiation state of monocyte-derived cells, which are characterized to promote angiogenesis and collagen formation. Moreover, the IL-10, an anti-inflammatory cytokine that is secreted by Tregs and iNK cells, modulate cardiac fibroblasts and protect left ventricular remodeling.

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  Figure 3. Characters of T and NK cells in clinical studies of heart injury. T and NK cells are increased in myocardium after myocardial injury. Myocardial injury in patients activate T-cells which subsequently home to the injured myocardium and modulate local inflammatory activity. Effector T-cells are detected to be increased within the myocardial microvasculature and release inflammatory mediators that contribute to further leukocyte infiltration. In cardiovascular diseases such as acute coronary syndromes and atherosclerosis, CD4+CD28null T-cells present in the blood in the context of acute coronary events during several months and secreted IFN-γ and TNF-α, as well as cytotoxic mediators in the blood. Which may cause vascular damage either directly by killing endothelial cells or indirectly through macrophage activation. During the myocardial injury, Tregs are established to migrate from peripheral to the inflamed tissue to suppress diverse types of immune reactions and the inflammatory responses, such as in suppressing CD4+ CD25- T-cells proliferation and pro-inflammatory cytokines production. However, these protective Tregs show higher frequency of apoptosis than health controls…