open access

https://doi.org/10.11501/3182208

https://hdl.handle.net/2115/51497

Cre/LoxPシステムを用いた発現調節可能なアデノウイルスベクターによる同種移植片長期生着を目指した、CTLA4IgG遺伝子療法

英語

2001-03-23

Hokkaido University

24p.

共著者あり。共著者名:Murakami Masaaki, Inobe Manabu, Tanaka Kumiko, Chikuma Shunsuke, Saito Izumu, Kanegae Yumi, Yasunami Yohichi, Nakano Masahiko, Yamashita Kenichiro, Todo Satoru, Uede Toshimitsu

CTL4IgG was shown to inhibit the costimulatory signal for T cell activation by interfering with the ligation of CD28 and B7-1 or B7-2. To inhibit various immune responses including acute cellular rejection of allografts, a certain level of serum CTLA4IgG should be maintained for an appropriate period. We previously reported the adenovirus vector containing CTLA4IgG, which we designated as Adex1CACTLA4IgG. Adex1CACTLA4IgG was able to maintain a significant level of serum CTLA4IgG for a long period upon intravenous injection, which in turn inhibited the various immune responses including protective immunity against insulting infectous agents. To overcome the inhibitory effect, we constructed a new type of adenovirus vector, Adex1CALoxCTLA4IgGLox by cloning CTLA4IgG cDNA between two lox P sequences under control of CAG promoter. We demonstrated that the administration of adenovirus vector containing Cre recombinase gene (Adex1CACre) at desired time induced Cre-mediated recombination within a gene derived from Adex1CALoxCTLA4IgGLox vector and the cDNA of CTLA4IgG was excised from the transduced gene, and terminated the expression of CTLA4IgG in vitro and in vivo. More importantly, we also demonstrated that the long acceptance of allografts was achieved after the termination of CTLA4IgG expression, while the immune response against adenovirus was restored.

2001-03-23

甲第5449号

博士(医学)

博士論文

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