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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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TRANSPLANTATION

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

From the Division of Hematology and Oncology and the Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Hyogo College of Medicine; and the First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.

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 graftversus-leukemia effect, while promoting thymic-dependent T-cell reconstitution after allogeneic BMT.


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