Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences
Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences
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减少致命的移植物抗宿主病：跨越微小组织相容性差异的培养小鼠骨髓移植
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发表时间：
1985
期刊：
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通讯作者：
S. Hellman
中科院分区：
文献类型：
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作者：
P. Mauch;J. Lipton;B. Hamilton;J. Obbagy;D. Nathan;S. Hellman
小鼠骨髓培养技术用于制备供者骨髓，以供骨髓移植时跨越微小的组织相容性复合体差异。以前的研究表明，θ-阳性细胞从这样的培养物中迅速丢失，并且跨越主要组织相容性复合体差异的培养骨髓的移植导致致死性移植物抗宿主病（GVHD）的发展延迟。在这项研究中，来自3天培养物的总共1至2 × 10（7）个非贴壁细胞（740至1560 CFU [集落形成单位]）被用作供体骨髓的来源。评价了三种菌株组合：LP/J转化为C57 BL/6; BIO.BR转化为CBA/J;以及C57 BL/6转化为LP/J。在培养之前，用受体脾细胞免疫供体小鼠，以增加移植物抗宿主应答。对于LP/J骨髓进入C57 BL/6小鼠，需要5 × 10（7）个供体脾细胞与骨髓一起沿着移植以诱导致死性GVHD。然而，对于BIO.BR到CBA/J和C57 BL/6到LP/J菌株组合，在不添加脾细胞的情况下观察到致死性GVHD。大多数接受新鲜骨髓的动物在移植后五周死于GVHD。在使用培养的骨髓的情况下，LP/J转化为C57 BL/6、BIO.BR转化为CBA/J和C57 BL/6转化为LP/J菌株组合的三个月存活率分别为80%、51%和93%。通过分析菌株组合之间的血红蛋白多态性，证实了接受培养骨髓的所有受体动物中的长期供体植入。这些结果表明，与跨越主要组织相容性复合体差异的移植相比，使用培养的细胞进行跨越次要组织相容性复合体差异的骨髓移植允许植入，同时降低致死性GVHD的风险。
The murine bone marrow culture technique was used to prepare donor marrow for bone marrow transplantation across minor histocompatibility complex differences. Previous studies have shown that theta-positive cells are rapidly lost from such cultures and that transplantation of cultured marrow across major histocompatibility complex differences results in a delay in the development of lethal graft-v-host disease (GVHD). In this study, a total of 1 to 2 X 10(7) nonadherent cells (740 to 1560 CFUs [colony-forming units]) from three-day-old cultures were used as a source of donor marrow. Three strain combinations were evaluated; LP/J into C57BL/6; BIO.BR into CBA/J; and C57BL/6 into LP/J. Donor mice were immunized with recipient spleen cells prior to culture in order to increase the graft-v-host response. For LP/J marrow into C57BL/6 mice, 5 X 10(7) donor spleen cells transplanted along with the marrow were needed to induce lethal GVHD. However, lethal GVHD was seen without the addition of spleen cells for BIO.BR into CBA/J and C57BL/6 into LP/J strain combinations. Most animals receiving fresh marrow were dead of GVHD five weeks after transplantation. With the use of cultured marrow the three-month survival was 80%, 51%, and 93%, respectively, for LP/J into C57BL/6, BIO.BR into CBA/J, and C57BL/6 into LP/J strain combinations. Long-term donor engraftment in all recipient animals receiving cultured marrow was confirmed by analyzing hemoglobin polymorphisms between the strain combinations. These results demonstrate that in contrast to transplantation across major histocompatibility complex differences, the use of cultured cells for bone marrow transplantation across minor histocompatibility complex differences allows for engraftment while reducing the risk of lethal GVHD.