Induction of immunological tolerance by cell adhesion moleculerelated substances.

细胞粘附分子相关物质诱导免疫耐受。

• 批准号: 04557020
• 负责人: UEDE Toshimitsu
• 金额: $ 10.94万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557020/
• 关键词: Transplantation; Rejection; Cell Adhesion Molecule; Immunological Torerance; CTLA4; 可溶性接着分子; 補助シグナル; アナヅィー; アナジィー

The purpose of this study was to generate soluble forms of cell adhesion molecules which can efficiently inhibit the costimulatory signals for T cell activation and proliferation. We generated a fusion protein consisting of a Fc portion of human IgG_1 or human IgM and an extracellular portion of mouse CTLA4 (CTLA4-IgG and CTLA4-IgM,respectively).CTLA4-IgM efficiently inhibited the T cell proliferation induced by mixed lymphocyte reaction (MLR) as compared to CTLA4-IgG.Furthermore, the combination of low does FK506 and CTLA4-IgM (2.3mug/ml) resulted in significant prolongation of cardiac allograft surviral (C57BL/6 into CBA/J), where as cardiac alloglaft surviral in recipients treated with FK506 plus CTLA4-IgG (2.3mug/ml) resulted in moderate prolongation of grafts.

本研究的目的是生成可溶形式的细胞粘附分子，可以有效地抑制T细胞活化和增殖的共刺激信号。我们生成了一种融合蛋白，由人IgG_1或人IgM的Fc部分和小鼠CTLA4的细胞外部分（分别为CTLA4- igg和CTLA4-IgM）组成。与CTLA4-IgG相比，CTLA4-IgM能有效抑制混合淋巴细胞反应（MLR）诱导的T细胞增殖。此外，低浓度FK506和CTLA4-IgM （2.3mug/ml）联合使用可显著延长同种异体心脏移植存活率（C57BL/6至CBA/J），而FK506 + CTLA4-IgG （2.3mug/ml）联合使用可适度延长移植物存活率。

项目成果

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Inobe,M.：“鉴定 B7 鼠同源物的选择性剪接形式。”

Wang,W.: "The induction of J11d antigen on double negative T cells of MRL/Mp-lpr/lpr mice by high does calcium ionophore." Autoimmunity. 14. 321-328 (1993)

Wang,W.：“高剂量钙离子载体对 MRL/Mp-lpr/lpr 小鼠双阴性 T 细胞的 J11d 抗原诱导”。

Tamiya, Y., Yamamoto, N.and Uede, T.: "Protective effect of monoclonal antibodies against LFA-1 and ICAM-1 on myocardial reperfusion injury following global ischemia in rat hearts." Immunopharmacology. 29. 53-63 (1995)

Tamiya, Y.、Yamamoto, N. 和 Uede, T.：“针对 LFA-1 和 ICAM-1 的单克隆抗体对大鼠心脏整体缺血后心肌再灌注损伤的保护作用。”

森川雅之: "移植と細胞接着" 細胞. 27. 8-13 (1995)

Masayuki Morikawa：“移植和细胞粘附”细胞。 27. 8-13 (1995)

Yamamoto,N.: "Prevention of post-ischemic reperfusion injury of cardiac tissues by a monoclomal antibody,R2-1A6." Immunopharmacology. (In press).

Yamamoto,N.：“通过单克隆抗体 R2-1A6 预防心脏组织缺血后再灌注损伤。”