ANALYSIS OF TRANSPLANTATION IMMUNOLOGY IN INTRASPLENIC HEPATOCYTE TRANSPLANTATION

脾内肝细胞移植的移植免疫学分析

• 批准号: 09671272
• 负责人: SAWA Masayuki
• 金额: $ 2.05万
• 依托单位: ASAHIKAWA MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671272/
• 关键词: INTRASPLENIC HEPATOCYTE TRANSPLANTATION; TRANSPLANTATION IMMUNOLOGY; ADHESION MOLECULE; CD80; CD86

Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyie transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the refection of transplanted hepatocytes, induction of donor-specific unresponsiveness to graft without compromising the host immune system would be ideal. We previously reported that the Fas-Fas ligand system plays a critical role in the CD28-independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti-CD80/86 monoclonal antibodies and anti-FasL monoclonal antibody may prolong the survival of transplanted allogeneic hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute

肝细胞移植是克服供肝短缺的一种有潜力的治疗方式，同种异体肝细胞移植的临床应用已被考虑。然而，同种异体肝细胞移植有两个主要问题：保护移植的肝细胞免受排斥反应和刺激存活细胞的快速增殖。在没有免疫抑制的情况下，同种异体肝细胞在移植后几天内迅速被排斥，即使在同种异体全肝移植后相对容易诱导免疫耐受。因此，在同种异体肝细胞移植和全肝移植后，似乎存在不同的排斥机制。为了克服移植肝细胞的反射，在不损害宿主免疫系统的情况下，诱导供者特异性的移植物无反应将是理想的。我们曾报道Fas-Fas配体系统在CD28非依赖性肝细胞排斥反应通路中起关键作用。因此，用CTLA4免疫球蛋白(CTLA4Ig)或抗CD80/86单抗和抗FasL单抗阻断排斥反应可延长移植肝细胞的存活时间。此外，给予肝细胞生长因子(HGF)可以促进同种异体肝细胞的增殖，这可能导致开发出功能正常的肝脏替代品。

项目成果

Kawahara T, Yagita H, Kasai S, Sawa M, Kato K, Okumura K, Futagawa S, Mito M: "Allogeneic hepatocyte transplantation: contribution of Fas-Fas ligand interaction to allogeneic hepatocyie rejection."Journal of Gastroenterology & Hepatology. 13 Suppl. S119-1

Kawahara T、Yagita H、Kasai S、Sawa M、Kato K、Okumura K、Futakawa S、Mito M：“同种异体肝细胞移植：Fas-Fas配体相互作用对同种异体肝细胞排斥的贡献。”胃肠病学杂志

川原敏靖、他: "Critical Role of Fas/Fas Ligand Interaction in CD28-Independent Pathway of Allogeneic Murine Hepatocyte Rejection" HEPATOLOGY. 26. 944-948 (1997)

Toshiyasu Kawahara 等人：“Fas/Fas 配体相互作用在同种异体鼠肝细胞排斥的 CD28 独立途径中的关键作用”《肝病学》26. 944-948 (1997)

Kawahara T, Yagita H, Okumura K, Futagawa S: "T cell-mediated effector mechanisms in the rejection of allogeneically transplanted hepatocyies."Transplantation Proceedings. Vol.31(1-2). 830-831 (1999)

Kawahara T、Yagita H、Okumura K、Futakawa S：“T 细胞介导的同种异体移植肝细胞排斥反应机制。”移植论文集。

川原敏靖: "Critical Role of Fas/Fas Ligand Interaction in CD28-Independent Pathway of Allogeneic Murine Hepatocyte Rejection" HEPATOLOGY. 26. 944-948 (1997)

Toshiyasu Kawahara：“Fas/Fas 配体相互作用在同种异体鼠肝细胞排斥的 CD28 独立途径中的关键作用”《肝病学》26. 944-948 (1997)。

Kawahara T.: "Tcell-mediated effector mechanisms in the rejection of allogeneically transplanted hepatocytes"Transplantation Proceedings. 31(1-2). 830-831 (1999)

Kawahara T.：“T细胞介导的同种异体移植肝细胞排斥反应机制”移植论文集。