Activated T Lymphocytes are Essential Drivers of Pathological Remodeling in Ischemic Heart Failure

作者：Bansal Shyam S; Ismahil Mohamed Ameen; Goel Mehak; Patel Bindiya; Hamid Tariq; Rokosh Gregg; Prabhu Sumanth D^*

来源：Circulation-Heart Failure, 2017, 10(3): e003688.

DOI：10.1161/CIRCHEARTFAILURE.116.003688

• adaptive immunity
• adoptive transfer
• heart failure
• inflammation
• T lymphocytes

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.

• 出版日期2017-3