Weiss L, Reich S, Slavin S
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Bone Marrow Transplant. 1996 May;17(5):789-92.
The effect of 15-deoxyspergualin (DSG) on bone marrow (BM) engraftment and graft-versus-host disease (GVHD) was studied in mice across both major (MHC) and minor (MiHC) histocompatibility barriers. (BALB/c x C57BL/6)F1 mice were inoculated with C57BL/6 cells, CBA mice were given B10.BR cells and BALB/c mice were transplanted with B10.D2 cells. All recipient mice were irradiated lethally or sublethally prior to transplantation. DSG had no effect on engraftment of parental cells in F1 mice at both 2.5 mg/kg and 10 mg/kg given daily for 10 days after treatment. Survival of F1 recipients of C57BL/6 cells increased significantly with 2.5 mg/kg DSG (p < 0.05). Across MiHC, 75% of DSG-treated CBA mice survived transplant for more than 150 days. No effect on GVHD was observed in the B10.D2 --> BALB/c setting. DSG abolished graft-versus-leukemia (GVL) effects in F1 mice transplanted with both BM and spleen cells (20%) of C57BL/6 mice and additionally inoculated with B cell leukemia (BCL1). In summary, in the semi-allogeneic murine models presented here DSG prevented GVHD but at the same time suppressed GVL effects induced by the allograft. For clinical use, DSG might therefore be very useful for prevention of GVHD post-allogeneic bone marrow transplantation for non-malignant diseases or for leukemia.
在跨越主要组织相容性复合体（MHC）和次要组织相容性复合体（MiHC）组织相容性屏障的小鼠中，研究了15-脱氧精胍菌素（DSG）对骨髓（BM）植入和移植物抗宿主病（GVHD）的影响。给（BALB/c×C57BL/6）F1小鼠接种C57BL/6细胞，给CBA小鼠注射B10.BR细胞，给BALB/c小鼠移植B10.D2细胞。所有受体小鼠在移植前接受致死性或亚致死性照射。在治疗后每天给予2.5mg/kg和10mg/kg的DSG，持续10天，DSG对F1小鼠中亲代细胞的植入没有影响。接受C57BL/6细胞的F1受体小鼠用2.5mg/kg DSG治疗后存活率显著提高（p<0.05）。在MiHC中，75%接受DSG治疗的CBA小鼠移植后存活超过150天。在B10.D2→BALB/c的情况下，未观察到DSG对GVHD有影响。在移植了C57BL/6小鼠的骨髓和脾细胞（20%）并额外接种B细胞白血病（BCL1）的F1小鼠中，DSG消除了移植物抗白血病（GVL）效应。总之，在此处呈现的半同种异体小鼠模型中，DSG预防了GVHD，但同时抑制了同种异体移植诱导的GVL效应。因此，对于临床应用，DSG可能对预防非恶性疾病或白血病的异基因骨髓移植后的GVHD非常有用。
