免疫系统衰老是促发心衰的重要因素，但原因和机制不清。我们前期发现：β1肾上腺素受体（β1-AR）自身抗体（β1-AA）阳性心衰患者外周血中存在有衰老的Treg；回输健康小鼠的Treg可改善β1-AA阳性小鼠心脏损伤。据此提出假说：β1-AA通过持续激活β1-AR引起Treg衰老，参与免疫衰老所致心衰。本研究拟利用小动物超声、流式细胞术、β-半乳糖苷酶活性检测等，观察β1-AA所致Treg衰老的变化特点及其在心衰发生发展中的贡献；通过细胞共培养、细胞因子芯片筛查、siRNA干扰等，阐明β1-AA诱导的衰老Treg参与心衰的直接和/或间接机制；利用荧光共振能量转移、二聚体上膜数量控制体系、质粒转染等，证实β1-AA通过增加β1-AR/β2-AR二聚化，导致β1-AR内吞障碍及其下游信号持续激活，最终诱导Treg衰老的分子机制。本项目旨在证明自身抗体引起的Treg衰老是导致心衰重要病因的新观点。

Aging of the immune system is an important factor in promoting heart failure, but the cause and mechanism are not clear. We previously found that there was senile Treg in peripheral blood of patients with heart failure who were beta 1-adrenergic receptor (beta 1-AR) autoantibody (beta 1-AA), and that transfusion of Treg into healthy mice could improve heart injury in beta 1-AA positive mice. It is hypothesized that beta 1-AA can induce Treg senescence by continuously activating beta 1-AR and participate in heart failure caused by immune senescence. The purpose of this study is to observe the characteristics of Treg aging induced by beta-AA and its contribution to the occurrence and development of heart failure by means of small animal ultrasound, flow cytometry and detection of beta-galactosidase activity, and to elucidate the direct and/or indirect mechanisms of Treg involvement in heart failure by means of co-culture of cells, cytokine chip screening and siRNA interference. The number control system of the upper membrane of the dimer and plasmid transfection confirmed that beta 1-AA could induce endocytosis and downstream signal activation of beta 1-AR by increasing beta 1-AR/beta 2-AR dimerization, and finally induce the molecular mechanism of Treg aging. The aim of this project is to prove that Treg aging induced by autoantibodies is an important cause of heart failure.