Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation
Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation
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DOI：
10.1182/blood-2003-12-4309
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发表时间：
2004-09-01
期刊：
影响因子：
20.3
通讯作者：
Sano, H
中科院分区：
文献类型：
--
作者：
Imado, T;Iwasaki, T;Sano, H
移植物抗宿主病（GVHD）是异基因骨髓移植（BMT）的主要并发症。当GVHD由T细胞耗尽的移植物或免疫抑制剂控制时，BM移植受者通常遭受白血病复发率增加和免疫重建受损。利用小鼠骨髓移植模型，我们研究了肝细胞生长因子（HGF）基因转染对移植物抗宿主病（GVHD）严重程度、移植物抗白血病效应和骨髓移植后T细胞重建的影响。HGF基因转移后，急性GVHD减少，而成熟的供体T细胞对宿主抗原的反应得以保留，导致无白血病生存率的显着提高。HGF基因转移促进骨髓来源的T细胞的再生和这些细胞对同种异体抗原的反应性。此外，HGF保留了GVHD小鼠胸腺细胞表型和胸腺基质结构。这表明HGF对胸腺具有强有力的保护作用，这反过来又促进了同种异体BMT后骨髓源性T细胞的重建。这些结果表明，HGF基因转染可以减少急性GVHD保留移植物抗白血病效应，同时促进胸腺依赖性T细胞重建后异基因BMT。(C)2004年，美国血液学会。
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. (C) 2004 by The American Society of Hematology.