目的:研究致敏性CD4n + T细胞在心肌梗死（心梗）后心肌重构中的作用。n 方法:①体外实验：提取原代小鼠脾脏CD4n + T细胞，用CD3/CD28抗体处理48 h后，超高速离心并提取细胞上清液中的外泌体。将致敏性CD4n + T细胞来源的外泌体与心肌成纤维细胞共同孵育48 h，利用细胞增殖及细胞毒性检测实验（CCK-8）、Transwell实验及免疫荧光实验检测致敏性CD4n + T细胞来源的外泌体对心肌成纤维细胞增殖、迁移及分化的影响。②体内实验：利用随机数字表法将40只雄性C57小鼠分成对照组（Ctrl组）、假手术组（Sham组）、心梗组（MI组）、外泌体处理组（MI+Exo组），每组10只。采用结扎冠状动脉左前降支复制小鼠心梗模型。MI+Exo组于制模后尾静注射外泌体40 μg/d。术后4周，用心脏超声、定量聚合酶链反应（qPCR）评估致敏性CD4n + T细胞来源的外泌体对小鼠心功能状态及心脏纤维化程度的影响。n 结果:①体外实验：致敏性CD4n + T细胞来源的外泌体可以显著增加心肌成纤维细胞增殖、迁移及分化能力〔细胞增殖（n A值）：0.31±0.01比0.21±0.01，迁移能力（个/MP）：79.20±3.34比48.80±2.13，分化能力（α-平滑肌肌动蛋白，α-SMA；荧光强度）：1.56±0.03比1.00±0.02，均n P<0.05〕。②体内实验：致敏性CD4n + T细胞来源的外泌体可加速心梗后心功能的恶化，表现为：与MI组比较，MI+Exo组左室射血分数（LVEF）及短轴收缩率（FS）显著下降〔LVEF：0.185±0.008比0.257±0.022，FS：（9.72±1.72）%比（14.08±1.08）%，均n P<0.05〕，左室舒张期末内径（LVEDD）及左室收缩期末内径（LVESD）显著增加〔LVEDD（mm）：5.43±0.29比4.62±0.35，LVESD（mm）：4.94±0.12比3.69±0.29，均n P<0.05〕。另外，qPCR结果显示，致敏性CD4n + T细胞来源的外泌体具有促进心梗后心肌纤维化的发生，表现为：MI+Exo组α-SMA、胶原（Col1a1、Col3a1）的mRNA表达显著高于MI组〔α-SMA（2n -ΔΔCT）：4.72±0.89比3.58±0.78，Col1a1（2n -ΔΔCT）：6.59±0.56比4.23±0.42，Col3a1（2n -ΔΔCT）：13.40±1.03比4.96±0.36，均n P<0.05〕。n 结论:致敏性CD4n + T细胞来源的外泌体具有显著加速心梗后心肌病理性重构的作用。n “,”Objective:To explore the role of activated CD4n + T cells in cardiac remodeling after myocardial infarction (MI).n Methods:① Experiment n in vitro: naive CD4n + T cells were isolated in mouse spleen, and then stimulated with plate-bound anti-CD3 and anti-CD28 for 48 hours. Exosomes isolated from the supernatant of activated CD4n + T cells were incubated with cardiac fibroblasts (CFs) for 48 hours, and then the ability of CFs proliferation, migration and differentiation were detected by cell counting kit-8 (CCK-8) assay, Transwell assay, and immunofluorescence assay. ② Experiment n in vivo: 40 male C57 mice were divided into 4 groups according to random number table method, including control group (Ctrl group), sham operation group (Sham group), MI group, and exosome treatment group (MI+Exo group), with 10 in each group. The mice model of MI was established by ligating the left anterior descending coronary artery. In MI+Exo group, 40 μg/d exosomes were injected intravenously into the tail after modeling. Cardiac function and cardiac fibrosis post-MI were assessed by echocardiography and quantitative polymerase chain reaction (qPCR) at 4th week.n Results:① n In vitro: exosomes derived from activated CD4n + T cells significantly promote CFs proliferation, migration and differentiation [proliferation ability (n A value): 0.31±0.01 vs. 0.21±0.01, migration capability (cells/MP): 79.20±3.34 vs. 48.80±2.13, differentiation ability (α-smooth muscle actin, α-SMA; fluorescence intensity): 1.56±0.03 vs. 1.00±0.02, alln P < 0.05]. ② n In vivo: echocardiographic analysis showed that exosomes derived from activated CD4n + T cells aggravated the deterioration of cardiac dysfunction post-MI than MI group, as indicated by left ventricular ejection fraction (LVEF) and fractional shortening (FS) decreased significantly [LVEF: 0.185±0.008 vs. 0.257±0.022, FS: (9.72±1.72)% vs. (14.08±1.08)%, both n P < 0.05], left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) increased significantly [LVEDD (mm): 5.43±0.29 vs. 4.62±0.35, LVESD (mm): 4.94±0.12 vs. 3.69±0.29, both n P < 0.05]. Additionally, qPCR showed that exosomes derived from activated CD4 n + T cells remarkably promoted myocardial fibrosis post-MI than MI group, as indicated by the mRNA expression of α-SMA, collagens (Col1a1, Col3a1) in MI+Exo group was significantly higher than that in MI group [α-SMA (2 n -ΔΔCT): 4.72±0.89 vs. 3.58±0.78, Col1a1 (2n -ΔΔCT): 6.59±0.56 vs. 4.23±0.42, Col3a1 (2n -ΔΔCT): 13.40±1.03 vs.4.96±0.36, all n P < 0.05].n Conclusion:Activated CD4n + T cells promote cardiac remodeling following MI through transferring exosomes to CFs.n