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

• Project/Area Number: 12671005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Juntendo University
• Principal Investigator: HIRANO takao Juntendo University school of medicine Dept. of Internal medicine Associate professor, 医学部, 助教授 (10165186)
• Co-Investigator(Kenkyū-buntansha): YAGITA hideo Juntendo University school of medicine Dept. of Immunology Associate professor, 医学部, 助教授 (30182306) ; OSHIMI kazuo Juntendo University school of medicine Dept. of Internal medicine Professor, 医学部, 教授 (40089991) ; MIYAJIMA hiroaki Juntendo University school of medicine Div. of Pathobiology Assistant professor, 医学部, 助手 (80209907) ; OKUMURA ko Juntendo University school of medicine Dept. of Immunology Professor, 医学部, 教授 (50009700)
• Project Period (FY): 2000 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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. Immunol. 164. 664-669 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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 murine acute and chronic graft-versus-host diseases"J Immunol. 167. 4981-4986 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
• [Publications] 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 (2001)