Differential effects of anti Fas ligand and anti TNF-alpha antibodies on GVHD pathologies

抗 Fas 配体和抗 TNF-α 抗体对 GVHD 病理的不同影响

• 批准号: 12671005
• 负责人: HIRANO takao
• 金额: $ 2.05万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671005/
• 关键词: HVG; GVH; metalloproteinase inhibitor; GVL; TNF-alpha; Fas; FasL; GVHD; MPI; HVGD; IL-4; メタロプロテナーゼインヒビター

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), that is a major complication after allogeneic bone marrow transplantation. We here examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 into irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect the hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.

肿瘤坏死因子（TNF）和Fas配体（FasL）与移植物抗宿主病（GVHD）的发病机制有关，这是同种异体骨髓移植后的主要并发症。我们在此检查了金属蛋白酶抑制剂 (KB-R7785) 在骨髓移植后抑制小鼠急性 GVHD 模型中 TNF-α 和 FasL 释放的改善作用。将 KB-R7785 注射到接受 C57BL/6 骨髓细胞和脾细胞的受辐射 (BALB/c x C57BL/6) F1 小鼠中，可降低死亡率和体重减轻，同时肝脏、肠道和造血系统中 GVHD 病理迹象极少组织。 KB-R7785治疗不影响供体细胞的造血重建。因此，KB-R7785可能成为骨髓移植后GVHD的有效治疗剂。

项目成果

Sakurai, J. et al.: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells"J. Immunol.. 164;2. 664-669 (2000)

Sakurai, J. 等人：“阻断 CTLA-4 信号可通过增强调节性 CD8 T 细胞的扩增来抑制 Th2 介导的小鼠慢性移植物抗宿主病”。

J. Sakurai, J. Ohata, K. Saito, H. Miyajima, T. Hirano, T. Kohsaka, S. Enomoto, K. Okumura, and M. Azuma: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells"J. Immu

J. Sakurai、J. Ohata、K. Saito、H. Miyajima、T. Hirano、T. Kohsaka、S. Enomoto、K. Okumura 和 M. Azuma：“CTLA-4 信号的阻断可抑制 Th2 介导的小鼠慢性病

Nozawa, K., et al.: "Preferential blocade of CD8+T cell responses by administration of anti-CD137 ligand moclonal antibody result in differential effect on development of murine acute and chronic graft-versus-host disease"J.Immunol.. 167;9. 4981-4986 (200

Nozawa, K. 等人：“通过施用抗 CD137 配体单克隆抗体优先产生 CD8 T 细胞反应，对小鼠急性和慢性移植物抗宿主病的发展产生不同的影响”J.Immunol.. 167

Nozawa, K. et al.: "Preferential blockade of CD8+ T Cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic"J. Immunol.. 167;9. 4981-4986 (2001)

Nozawa, K. 等人：“通过施用抗 CD137 配体单克隆抗体优先阻断 CD8 T 细胞反应，对小鼠急性和慢性疾病的发展产生不同的影响”J.

K. Nozawa, J. Ohata, J. Sakurai, H. Hashimoto, H. Miyajima, H. Yagita, K. Okumura, and M. Azuma: "Preferential blockade of CD8(+) T cell responses by administration of anti-CD 137 ligand monoclonal antibody results in differential effect on development of

K. Nozawa、J. Ohata、J. Sakurai、H. Hashimoto、H. Miyajima、H. Yagita、K. Okumura 和 M. Azuma：“通过施用抗 CD 137 优先阻断 CD8( ) T 细胞反应