【摘 要】
：
目的：T淋巴细胞紊乱和自身抗体的存在是心衰恶化的重要免疫学机制,β1肾上腺素受体自身抗体(β1AA)在心衰患者血清中呈高阳性率、高滴度分布,用免疫吸附法将其去除后,患者的心功能明显改善、同时调节性T淋巴细胞(Treg cells)的数目也显著增多.CD4+CD25+nTreg cells的数量和功能与患者的心功能正相关,其异常也是CD4+T cells亚群失衡及自身抗体产生的重要因素.β1AA可诱
【机 构】
：
首都医科大学基础医学院生理与病理生理学系,北京,100069 中国医学科学院基础医学研究所生理与病
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目的：T淋巴细胞紊乱和自身抗体的存在是心衰恶化的重要免疫学机制,β1肾上腺素受体自身抗体(β1AA)在心衰患者血清中呈高阳性率、高滴度分布,用免疫吸附法将其去除后,患者的心功能明显改善、同时调节性T淋巴细胞(Treg cells)的数目也显著增多.CD4+CD25+nTreg cells的数量和功能与患者的心功能正相关,其异常也是CD4+T cells亚群失衡及自身抗体产生的重要因素.β1AA可诱发小鼠发生心衰并伴随CD4+T cells的过度激活,且β1AA可促进T cells的增殖和分泌.但β1AA是否可通过影响Treg cells进而参与心衰的病理进程还是未知.因此,本研究旨在观察β1AA对nTreg cells分化和功能的影响,并进一步探究其可能性改变对心肌细胞存亡的意义.方法：用β1AR单克隆抗体分别对健康BALB/c小鼠和裸鼠被动免疫8周,检测模型鼠血清中与nTreg cells分化和免疫负性功能发挥相关的细胞因子变化；用β1AA分别作用于Th0 cells和nTreg cells,探讨β1AA对nTreg cells分化、分泌和体外抑制功能的影响；将经β1AA作用48h后的nTreg cells上清与H2O2共同作用心肌细胞,观察β1AA对nTreg cells细胞对心肌保护功能的影响.结果：β1AA分别通过上调IL-2/IL-2R、TGF-β和CTLA-4、IL-10/IL-10 R的表达促进健康BALB/c小鼠Treg cells的分化和活化；β1AA可通过β1AR途径促进经anti-CD3/CD28激活的ThO向CD4+CD25+ nTreg分化,且β1AA的浓度越高对ThO向nTreg的促分化作用的影响越强；β1AA对nTregs免疫负性调节功能的影响与β1AA的浓度相关；经较高浓度β1AA作用后的nTregs上清对心肌细胞的保护作用明显降低.结论：β1AA可促进健康BALB/c小鼠Treg cells活化,同时β1AA可在离体水平直接通过β1AR途径诱导nTreg cells分化；较高浓度的β1AA可抑制nTreg cells活化,并削减nTregs cells对心肌细胞的保护作用.
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