Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester.
Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester.
复制标题
通过用 L-亮氨酰-L-亮氨酸甲酯处理供体细胞来预防致命的小鼠移植物抗宿主疾病。
DOI：
10.1172/jci112730
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Lipsky,PE
中科院分区：
文献类型：
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作者：
Charley,M;Thiele,DL;Bennett,M;Lipsky,PE
移植物抗宿主病（GVHD）仍然是与骨髓移植相关的主要问题之一。进行当前的研究以确定用抗细胞毒性细胞化合物L-亮氨酰-L-亮氨酸甲酯（Leu-Leu-OMe）处理供体接种物是否会改变小鼠模型中GVHD的发展。移植了来自初始半同种异体供体的对照骨髓和脾细胞的混合物的辐照受体小鼠迅速死于GVHD，而用250 μ M Leu-Leu-OMe孵育的细胞的受体全部存活。此外，Leu-Leu-OMe处理从针对宿主同种异体抗原免疫的供体获得的细胞导致显著延长的存活。来自接受Leu-Leu-OMe处理的细胞并存活的各组小鼠的脾细胞的表型表征一致地揭示了供体表型。用250 μ M Leu-Leu-OMe处理骨髓细胞似乎对干细胞功能没有不良影响。通过脾5-碘-2 '-脱氧尿苷-125 I摄取测定，红细胞生成未减少。此外，粒细胞和巨核细胞的再生在对照或Leu-Leu-OMe处理的细胞的接受者的脾脏中在组织学上是等同的。因此，用Leu-Leu-OMe处理供体接种物可以防止这种小鼠品系组合中的GVHD，而没有明显的干细胞毒性。图片
Graft vs. host disease (GVHD) remains one of the main problems associated with bone marrow transplantation. The current studies were undertaken to determine whether treatment of the donor inoculum with the anticytotoxic cell compound L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) would alter the development of GVHD in a murine model. Irradiated recipient mice transplanted with a mixture of control bone marrow and spleen cells from naive semiallogeneic donors died rapidly from GVHD, whereas the recipients of cells incubated with 250 microM Leu-Leu-OMe all survived. In addition, Leu-Leu-OMe treatment of cells obtained from donors immunized against host alloantigens resulted in significantly prolonged survival. Phenotypic characterization of spleen cells from the various groups of mice that had received Leu-Leu-OMe-treated cells and survived consistently revealed the donor phenotype. Treatment of marrow cells with 250 microM Leu-Leu-OMe appeared to have no adverse effects on stem cell function. Erythropoiesis was undiminished, as assayed by splenic 5-iodo-2'-deoxyuridine-125I uptake. Moreover, granulocytic and megakaryocytic regeneration were histologically equivalent in the spleens of recipients of control or Leu-Leu-OMe-treated cells. Treatment of the donor inoculum with Leu-Leu-OMe thus prevents GVHD in this murine strain combination with no apparent stem cell toxicity.Images