Despite emerging data indicating a role for T cells in profibrotic cardiac repair and healing after ischemia, little is known about whether T cells directly impact cardiac fibroblasts (CFBs) to promote cardiac fibrosis (CF) in nonischemic heart failure (HF). Recently, we reported increased T cell infiltration in the fibrotic myocardium of nonischemic HF patients, as well as the protection from CF and HF in TCR-α^−/− mice. Here, we report that T cells activated in such a context are mainly IFN-γ⁺, adhere to CFB, and induce their transition into myofibroblasts. Th1 effector cells selectively drive CF both in vitro and in vivo, whereas adoptive transfer of Th1 cells, opposite to activated IFN-γ^−/− Th cells, partially reconstituted CF and HF in TCR-α^−/− recipient mice. Mechanistically, Th1 cells use integrin α4 to adhere to and induce TGF-β in CFB in an IFN-γ–dependent manner. Our findings identify a previously unrecognized role for Th1 cells as integrators of perivascular CF and cardiac dysfunction in nonischemic HF.

尽管新出现的数据表明T细胞在缺血后纤维化心脏修复和愈合中的作用，但对于T细胞是否直接影响心脏成纤维细胞（CFBs）促进非缺血性心力衰竭（HF）中的心脏纤维化（CF）知之甚少。最近，我们报道了非缺血性HF患者的纤维化心肌中T细胞浸润的增加，以及对TCR-α ^-/-小鼠的CF和HF的保护作用。在这里，我们报告说，在这种情况下激活的T细胞主要是IFN-γ ⁺，粘附在CFB上，并诱导它们转变为成肌纤维细胞。Th1效应细胞在体外和体内选择性驱动CF，而与活化的IFN-γ ^-/- Th细胞相反，Th1细胞的过继转移会部分重建TCR-α中的CF和HF^-/-受体小鼠。从机制上讲，Th1细胞使用整联蛋白α4以IFN-γ依赖性方式粘附并诱导CFB中的TGF-β。我们的发现确定了Th1细胞在非缺血性HF中作为血管周围CF和心脏功能障碍的整合者的先前未被认识的作用。