Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation
Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation
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DOI：
10.1053/bbmt.2002.v8.pm11939602
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发表时间：
2002-01-01
影响因子：
4.3
通讯作者：
Fuchs, EJ
中科院分区：
文献类型：
--
作者：
Luznik, L;Engstrom, LW;Fuchs, EJ
已经对环磷酰胺（CY）进行了广泛的研究，以进行免疫抑制特性，并且经常与人体相同的同种异体血液或骨髓移植（AlloBMT）在人类中与总体辐照（TBI）相结合。因为在移植后给药时，CY在抑制宿主 - 移植反应方面最有效（Mayumi H等人移植Proc。1986; 18：363-369），我们研究了移植后CY是否可以防止拒绝同种元。在用低剂量TBI调理的小鼠中。在小鼠模型中，移植后CY将TBI的剂量从500 CGY降低至小于或等于200 CGY，用于在100％的受体中植入1000万个主要的组织相容性复合物（MHC） - 相同的骨髓细胞。在用低剂量TBI和移植后CY的动物中，供体嵌合。与TBI的剂量成正比，存在于多个造血谱系中，并且与供体 - 应变皮肤移植物的无限生存有关。相比之下，单独使用TBI或单独移植后CY的动物无法在同倍体后获得植入，并含有抗多onor细胞毒性T细胞。尽管= 5000万个MHC认同的细胞和进行移植后CY，但添加低剂量TBI会降低同胞菌流所需的供体细胞的剂量，并将长期供体嵌合主义增加到> 50％。这些数据表明，低剂量的TBI和移植后CY合作，以防止在移植标准剂量的MHC-认同骨髓细胞后移植排斥反应。
Cyclophosphamide (Cy) has been studied extensively for its immunosuppressive properties and is frequently combined with total body irradiation (TBI) as conditioning prior to HILA-identical allogeneic blood or marrow transplantation (alloBMT) in humans. Because Cy is most effective at suppressing host-versus-graft reactions when the drug is given after the transplantation (Mayumi H et al. Transplant Proc. 1986;18:363-369), we investigated whether posttransplantation Cy could prevent rejection of allogeneic marrow in mice conditioned with low-dose TBI. In a mouse model, posttransplantation Cy reduced the dose of TBI required from 500 cGy to less than or equal to 200 cGy for the engraftment of 10 million major histocompatibility complex (MHC)-identical marrow cells in 100% of recipients. In animals conditioned with low-dose TBI and posttransplantation Cy, donor chimerism. was proportional to the dose of TBI, was present in multiple hematopoietic lineages, and was associated with the indefinite survival of donor-strain skin grafts. In contrast, animals conditioned with either TBI alone or posttransplantation Cy alone failed to achieve engraftment after alloBMT and contained antidonor cytotoxic T-cells. Although = 50 million MHC-identical cells and administering posttransplantation Cy, the addition of low-dose TBI reduced the dose of donor cells required for alloengraftment and increased long-term donor chimerism to >50%. These data demonstrate that low-dose TBI and posttransplantation Cy cooperate to prevent graft rejection following the transplantation of standard doses of MHC-identical marrow cells.