The development of the treatment of autoimmune diseases by cytokine gene transfer

细胞因子基因转移治疗自身免疫性疾病的研究进展

• 批准号: 07457122
• 负责人: MIYASAKA Nobuyuki
• 金额: $ 4.54万
• 依托单位: TOKYO MEDICAL & DENTAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457122/
• 关键词: cytokine; autoimmune disease; gene therapy

(1) Establishment of myelin basic protein (MBP)-specific T cell lines ;Lymph node cells were obtained from Lewis rats immunized with MBP peptide (68-88) and cultured with a repetitive stimulation with MBP and interleukin 2. T cell lines thus obtained were transfered to naive syngeneic rats and the induction of encephalomyelitis (experimental allergic encephalomyelitis ; EAE) was confirmed.(2) Transfer of cytokine genes to T cell lines ;Expression vectors for cytokine genes (IL-4, IL-10, TGFbeta) were prepared and transfected into COS cells. The culture supernatants were confirmed to have corresponding cytokine activities and those from TGFbeta-transfected COS cells strongly inhibited the proliferation of MBP-stimulated T cell lines in vitro. These cell lines were transferred into Lewis rats immunized with MBP peptide to examine whether cytokine-gene transfer successfully inhibit the induction of EAE.

(1)髓鞘碱性蛋白（MBP）特异性T细胞系的建立：从用MBP肽（68-88）免疫的刘易斯大鼠获得淋巴结细胞，并用MBP和白细胞介素2重复刺激培养。将由此获得的T细胞系转移到幼稚的同基因大鼠中，证实了脑脊髓炎（实验性变态反应性脑脊髓炎; EAE）的诱导。(2)将细胞因子基因转移至T细胞系;制备细胞因子基因（IL-4、IL-10、TGF β）的表达载体并转染至COS细胞中。结果表明，转染TGF β的COS细胞培养上清具有相应的细胞因子活性，并能显著抑制MBP刺激的T细胞系的增殖。将这些细胞系转移到用MBP肽免疫的刘易斯大鼠中，以检查是否成功地抑制了EAE的诱导。

项目成果

Mizushima N,et al.: "Ceramide induced apoptosis via CPP32 activation." FEBS Letters. 395. 267-271 (1996)

Mizushima N 等人：“神经酰胺通过 CPP32 激活诱导细胞凋亡。”