Induction of tolerance and suppression of rejection by transfer of immature hepatic dendritic cells.

通过转移未成熟的肝树突状细胞诱导耐受并抑制排斥反应。

• 批准号: 07557202
• 负责人: UEDE Toshimitsu
• 金额: $ 4.35万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557202/
• 关键词: CTLA4Ig; dendritic cells; small bowel transplantation; Kidney transplantation; Adenovirus vector; 皮膚移植; passenger leukocyte; 肢移植; GM-CSF; DST; キメリズム; 免疫学的寛容

(1) Immunological tolerance was achieved by intravenous injection of CTLA41g (100mug/head) for 7days in rat small bowel allografts. Long survival (>100days) of allografed small bowel was achieved in rat system. Increased serum levels of IL-4 and IL-10 were defected in tolerant rats, indicating that the Th2 type anti-allogeneic immune response favors the survival of allografted tissue.(2) Immunological tolerance was also achieved by intravenous injection of CTLA4Ig in rat kidney allografts. However, injection of allogeneic splenic dendritic cells or CTLA4Ig-treated dendritic cells failed to induce tolerance or long survival of allografted Kidney.(3) We generated adenovirus vectors containig CTLA4Ig, which can be used for the in vivo and in vitro production of CTLA4Ig.

(1)CTLA 41 g（100 μ g/头）静脉注射7天，可使大鼠小肠移植物获得免疫耐受。大鼠移植小肠可长期存活（> 100天）。耐受大鼠血清IL-4和IL-10水平升高，表明Th 2型抗同种异体免疫应答有利于同种异体移植组织的存活。(2)静脉注射CTLA 4 Ig也可使大鼠移植肾产生免疫耐受。然而，注射同种异体脾树突状细胞或CTLA 4 Ig处理的树突状细胞未能诱导同种异体移植肾的耐受或长期存活。(3)我们成功地构建了含CTLA 4 Ig的腺病毒载体，可用于体内和体外生产CTLA 4 Ig。

项目成果

Hara, T.: "Involvement of common 10 amino acid segment in the cytoplasmic region of CD40, but defferent MAP kinase in defferent CD40-mediated responses." Biochem.Biophys.Res.Commun.233. 187-192 (1997)

Hara, T.：“CD40 细胞质区域共有 10 个氨基酸片段，但不同的 MAP 激酶参与不同的 CD40 介导的反应。”

Tsuchida,Y.: "Limb allografts in rats treated with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies." J.Reconst.Microsurg.13. 107-110 (1997)

Tsuchida,Y.：“用抗 ICAM-1 和抗 LFA-1 单克隆抗体处理的大鼠同种异体肢体移植物。”

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

Tamiya, Y.：“针对 LFA 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。”

Hara,T.: "Involvement of a common 10-amino-acid segment in the cytoplasmic region of CD40 but different MAP kinases in different CD40-mediated responses." Biochem.Biophys.Res.Commun.233. 187-192 (1997)

Hara,T.：“CD40 细胞质区域有一个共同的 10 个氨基酸片段，但不同的 MAP 激酶参与了不同的 CD40 介导的反应。”

Inobe, M., Aoki, N., Linsley, P.S., Ledbetter, J.A., Abe, R,Murakami, M.and Uede, T.: "The role of B7-la molecule, an alternatively spliced form of murine B7-1 (CD80), on T cell activation." J.Immunol.157. 582-588 (1996)

Inobe, M.、Aoki, N.、Linsley, P.S.、Ledbetter, J.A.、Abe, R、Murakami, M. 和 Uede, T.：“B7-1a 分子（鼠 B7-1 的选择性剪接形式）的作用