Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation.
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.
Imado
Takehito
T
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Iwasaki
Tsuyoshi
T
Kataoka
Yasuro
Y
Kuroiwa
Takanori
T
Hara
Hiroshi
H
Fujimoto
Jiro
J
Sano
Hajime
H
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000276:immunology; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000188:drug therapy; D020544:Graft vs Leukemia Effect / Q000187:drug effects* / Q000276:immunology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
D001324:Autoantigens; D017228:Hepatocyte Growth Factor