Activated T lymphocytes are essential drivers of pathological remodeling in ischemic heart failure

Academic Article


  • Background - Inappropriately sustained inflammation is a hallmark of chronic ischemic heart failure (HF); however, the pathophysiological role of T lymphocytes is unclear. Methods and Results - Permanent coronary ligation was performed in adult C57BL/6 mice. When compared with sham-operated mice, mice with HF (8 weeks after ligation) exhibited the following features: (1) significant (P<0.05) expansion of circulating CD3 CD8 cytotoxic and CD3 CD4 helper (Th) T lymphocytes, together with increased Th1, Th2, Th17, and regulatory T-cell (Treg) CD4 subsets; (2) significant expansion of CD8 and CD4 T cells in failing myocardium, with increased Th1, Th2, Th17, and Treg CD4 subsets, marked reduction of the Th1/Th2 ratio, augmentation of the Th17/Treg ratio, and upregulation of Th2 cytokines; and (3) significantly increased Th1, Th2, Th17 cells, and Tregs, in the spleen and mediastinal lymph nodes, with expansion of splenic antigen-experienced effector and memory CD4 T cells. Antibody-mediated CD4 T-cell depletion in HF mice (starting 4 weeks after ligation) reduced cardiac infiltration of CD4 T cells and prevented progressive left ventricular dilatation and hypertrophy, whereas adoptive transfer of splenic CD4 T cells (and, to a lesser extent, cardiac CD3 T cells) from donor mice with HF induced long-term left ventricular dysfunction, fibrosis, and hypertrophy in naive recipient mice. Conclusions - CD4 T lymphocytes are globally expanded and activated in chronic ischemic HF, with Th2 (versus Th1) and Th17 (versus Treg) predominance in failing hearts, and with expansion of memory T cells in the spleen. Cardiac and splenic T cells in HF are primed to induce cardiac injury and remodeling, and retain this memory on adoptive transfer. + + + + + + + + + + + + + +
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Bansal SS; Ismahil MA; Goel M; Patel B; Hamid T; Rokosh G; Prabhu SD
  • Volume

  • 10
  • Issue

  • 3