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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1542-1549.
Prepublished online as a Blood First Edition Paper on April 20, 2004; DOI 10.1182/blood-2003-12-4309.
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Submitted December 18, 2003
Accepted April 8, 2004
Hepatocyte Growth Factor Preserves Graft-Versus-Leukemia Effect and T cell Reconstitution After Marrow Transplantation
Takehito Imado, Tsuyoshi Iwasaki*, Yasuro Kataoka, Takanori Kuroiwa, Hiroshi Hara, Jiro Fujimoto, and Hajime Sano
Division of Hematology and Oncology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
* Corresponding author; email: tsuyo-i{at}hyo-med.ac.jp.
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, BMT 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 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 allo-antigens. 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.
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