郑海清，陈壮桂，刘秋莉，陈小湧，彭延文，胡昔权.CD8+CD28-T淋巴细胞在骨髓间充质干细胞治疗实验性自身免疫性脑脊髓炎小鼠中的免疫调[J].中华物理医学与康复杂志,2016,38(9):641-646
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| CD8+CD28-T淋巴细胞在骨髓间充质干细胞治疗实验性自身免疫性脑脊髓炎小鼠中的免疫调 |
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| DOI： |
| 中文关键词: 多发性硬化 间充质干细胞 CD8+CD28-调节性T细胞 |
| 英文关键词: Multiple sclerosis Mesenchymal stem cells CD8+CD28- regulatory T cells |
| 基金项目:国家自然科学基金（81572228）；广东省自然科学基金（2015A030313015）；中山大学高校青年教师培育项目（15ykpy26） |
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| 中文摘要: |
| 目的探讨CD8+CD28-T淋巴细胞在骨髓间充质干细胞(MSCs)治疗实验性自身免疫性脑脊髓炎小鼠中的免疫调节作用。 方法采用6~8周、体重16~20g的C57 BL/6雌性小鼠28只，MOG35-55作为免疫诱导剂，构建实验性自身免疫性小鼠模型(EAE)。将28只EAE小鼠随机分成4组：PBS治疗组、MSC低剂量治疗组（2×105个/只）、MSC中剂量治疗组（1×106个/只）、MSC高剂量治疗组（5×106个/只），每组7只。各治疗组均于建模后第15天经尾静脉注射健康人来源的MSCs，对照组注射磷酸盐缓冲液（PBS）。 随后每日进行神经功能评分及测量体重，于治疗30d后处理动物，取材进行相关神经病理学及细胞免疫学分析。 结果不同剂量的MSCs均较PBS能有效地促进EAE小鼠神经功能的恢复（P<0.05），且MSCs中剂量治疗更能显著促进EAE小鼠神经功能的恢复。各MSCs治疗组小鼠脾脏细胞中CD8+CD28-调节性T细胞的数量均较PBS治疗组的表达有所增加，但其分泌的IL-10水平较PBS治疗组差异无统计学意义（P>0.05）。 结论CD8+CD28-调节性T细胞可能不是MSCs促进EAE小鼠神经功能恢复的主要效应细胞，可能只是起到协同治疗作用。 |
| 英文摘要: |
| Objective To study the immune system regulatory effects of CD8+CD28- regulatory T lymphocytes in an experimental bone marrow mesenchymal stem cell treatment of autoimmune encephalomyelitis. Methods A model of autoimmune encephalomyelitis (EAE) was established in twenty-eight C57BL/6 female mice, 6 to 8 weeks old weighing 16 to 20 g using myelinoligodendrocyte glycoprotein 35-55 amino acid peptide (MOG35-55). The mice were randomly divided into a phosphate-buffered solution (PBS) group (n=7), an MSCs-Low group ［n=7 which received an injection of 2×105 mesenchymal stem cells (MSCs)］, an MSCs-Med group (n=7, 1×106 MSCs), and an MSCs-High group (n=7, 5×106 MSCs). Their clinical condition was then evaluated daily. On the 15th day after the MOG35-55 immunization, the different MSC doses were administered intravenously via the tail. On the 30th day the mice were sacrificed to observe any neuropathology of the spinal cord. At the same time, FACS flow cytometry was used to assay CD8+CD28- T cells in the spleen. ResultsCompared with the PBS control group, the MSC treatment effectively alleviated illness among the mice by the 15th day after the immunization. The maximum and average disease scores and clinical illness scores had all improved significantly. The medium dosage worked best. Neuropathological analysis showed that the MSC treatment could significantly reduce the invasion of inflammatory cells and minimize demyelination in the spinal cord. Furthermore, the CD8+CD28- regulatory T cells in the spleens of the MSC-treated animals increased compared with the PBS control group, though the secreted levels of IL-10 showed no obvious difference. ConclusionsTreatment with MCSs can promote the recovery of neural function in autoimmune encephalomyelitis, at least in mice. CD8+CD28- regulatory T cells may not be the main effector cells, playing only a synergistic therapeutic role. |
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