Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation.

Abstract

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). When GVHD is controlled by T-cell-depleted grafts or immunosuppressants, BM transplant recipients often suffer from an increased rate of leukemic relapse and impaired reconstitution of immunity. Using a mouse BMT model, we investigated the effects of hepatocyte growth factor (HGF) gene transfection on the severity of GVHD, the graft-versus-leukemia effect, and the reconstitution of T cells after BMT. After HGF gene transfer, acute GVHD was reduced, while mature donor T-cell responses to host antigens were preserved, resulting in a significant improvement of leukemia-free survival. HGF gene transfer promoted regeneration of bone marrow-derived T cells and the responsiveness of these cells to alloantigens. Furthermore, HGF preserved the thymocyte phenotype and thymic stromal architecture in mice with GVHD. This suggested that HGF exerts a potent protective effect on the thymus, which in turn promotes reconstitution of bone marrow-derived T cells after allogeneic BMT. These results indicate that HGF gene transfection can reduce acute GVHD preserving the graft-versus-leukemia effect, while promoting thymic-dependent T-cell reconstitution after allogeneic BMT.

• Authors: Takehito Imado, Tsuyoshi Iwasaki, Yasuro Kataoka, Takanori Kuroiwa, Hiroshi Hara, Jiro Fujimoto, Hajime Sano
• Journal: Blood (Blood) Vol. 104 Issue 5 Pg. 1542-9 (Sep 01 2004) ISSN: 0006-4971 [Print] United States
• PMID: 15100150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Hepatocyte Growth Factor

Topics

• Animals
• Autoantigens (immunology)
• Bone Marrow Transplantation
• Cell Division (immunology)
• Disease-Free Survival
• Graft vs Host Disease (drug therapy)
• Graft vs Leukemia Effect (drug effects, immunology)
• Hepatocyte Growth Factor (pharmacology)
• Immunity, Cellular (drug effects, immunology)
• Leukemia (drug therapy, immunology, mortality)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• T-Lymphocytes (cytology, drug effects, immunology)
• Thymus Gland (cytology, immunology)
• Transplantation, Homologous