Background Despite the emerging association between Heart Failure (HF) and inflammation, the role of T cells, major players in chronic inflammation, has only recently begun to be explored. Whether T cell recruitment to the left ventricle (LV) participates in the development of HF requires further investigation to identify novel mechanisms that may serve for the design of alternative therapeutic interventions. Methods and Results Real time videomicroscopy of T cells from non- ischemic HF patients or from mice with HF induced by transverse aortic constriction (TAC) revealed enhanced adhesion to activated vascular endothelial cells under flow conditions in vitro compared with T cells from healthy subjects or sham mice. T cells in the mediastinal lymph nodes and the intramyocardial endothelium were both activated in response to TAC and the kinetics of LV T cell infiltration was directly associated with the development of systolic dysfunction. In response to TAC, T cell deficient mice (TCRα−/−) had preserved LV systolic and diastolic function, reduced LV fibrosis, hypertrophy and inflammation, and improved survival compared to WT mice. Furthermore T cell depletion in WT mice after TAC prevented HF. Conclusions T cells are major contributors to non-ischemic HF. Their activation combined with the activation of the LV endothelium results in LV T cell infiltration negatively contributing to HF progression through mechanisms involving cytokine release and induction of cardiac fibrosis and hypertrophy. Reduction of T cell infiltration is thus identified as a novel translational target in HF.

Inhibiting FN polymerization or cardiac fibroblast gene expression attenuates pathological properties of MFs in vitro and ameliorates adverse cardiac remodeling and fibrosis in an in vivo model of heart failure. Interfering with FN polymerization may be a new therapeutic strategy for treating cardiac fibrosis and heart failure.

T cell–mediated inflammation is associated with heart failure, but how heart-infiltrated T cells impact cardiac function remains unknown. Nevers et al. demonstrate that IFN-γ–producing T helper cells interact with cardiac fibroblasts to mediate cardiac fibrosis and dysfunction.

Background--Left ventricular dysfunction and heart failure are strongly associated in humans with increased circulating levels of proinflammatory cytokines, T cells, and soluble intercellular cell adhesion molecule 1 (ICAM1). In mice, infiltration of T cells into the left ventricle contributes to pathological cardiac remodeling, but the mechanisms regulating their recruitment to the heart are unclear. We hypothesized that ICAM1 regulates cardiac inflammation and pathological cardiac remodeling by mediating left ventricular T-cell recruitment and thus contributing to cardiac dysfunction and heart failure.