Engraftment of severe combined immune deficient mice receiving allogeneic bone marrow via in utero or postnatal transfer
Engraftment of severe combined immune deficient mice receiving allogeneic bone marrow via in utero or postnatal transfer
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DOI：
10.1182/blood.v92.10.3949.422k26_3949_3959
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发表时间：
1998-11-15
期刊：
影响因子：
20.3
通讯作者：
Vallera, DA
中科院分区：
文献类型：
--
作者：
Blazar, BR;Taylor, PA;Vallera, DA
虽然子宫内移植（IUT）已被证明是治疗人类严重联合免疫缺陷（SCID）的有效方法，但与产后骨髓移植（BMT）相比，子宫内移植（IUT）治疗SCID的相对优点尚不清楚。因此，在小鼠中进行了比较研究，以确定这两种情况下的植入结果。由于t细胞耗损（TCD）降低了移植物抗宿主病（GVHD）的严重程度，但损害了同种异体移植，因此对TCD或非TCD骨髓进行了研究，并使用组织评分系统和通过将移植小鼠的脾细胞过继转移到继发受体中来评估GVHD的风险。非scid受者接受bmt前照射，以模拟同种异体移植所需的条件。非TCD，特别是TCD BM细胞的IUT受者通常比非条件SCID受者有更高水平的供体t细胞和髓系外周血（PB）植入。成年SCID受者TCD或非TCD BM细胞数量增加导致与IUT受者相似的PB植入水平。然而，在这些条件下，GVHD平均评分高于IUT接受者。大多数来自IUT受体的脾细胞过继移植受体是无gvhd的，这与体外对宿主异体抗原耐受的证据一致。与IUT受体相比，接受全身照射（TBI）治疗的小鼠胸腺损伤的证据表明，与IUT受体相比，胸腺和脾脏具有记忆表型的T细胞比例更高。IUT小鼠在3周龄时胸腺有强烈的重建。我们的数据表明，与产后BMT相比，IUT具有许多优势。未来的研究表明免疫重建在IUT和产后BMT中的精细特异性。(C) 1998年由美国血液病学会出版。
Although in utero transplantation (IUT) has been shown to be effective in treating human severe combined immune deficiency (SCID), the relative merit of IUT as compared with postnatal bone marrow transplantation (BMT) for SCID is unknown. Therefore, comparative studies were undertaken in mice to determine the engraftment outcome in these two settings. Because T-cell depletion (TCD) reduces graft-versus-host disease (GVHD) severity but compromises alloengraftment, studies were performed with TCD or non-TCD BM and GVHD risk was assessed using a tissue scoring system and by the adoptive transfer of splenocytes from engrafted mice into secondary recipients. Non-SCID recipients received pre-BMT irradiation to simulate those circumstances in which conditioning is required for alloengraftment. IUT recipients of non-TCD and especially TCD BM cells in general had higher levels of donor T-cell and myeloid peripheral blood (PB) engraftment than nonconditioned SCID recipients. Increased TCD or non-TCD BM cell numbers in adult SCID recipients resulted in similar levels of PB engraftment as IUT recipients. However, under these conditions, mean GVHD scores were higher than in IUT recipients. The majority of adoptive transfer recipients of splenocytes from IUT recipients were GVHD-free, consistent with the in vitro evidence of tolerance to host alloantigens. Total body irradiation (TBI)-treated mice that had the highest engraftment had evidence of thymic damage as denoted by a higher proportion of thymic and splenic T cells with a memory phenotype as compared with IUT recipients. IUT mice had vigorous thymic reconstitution by 3 weeks of age. Our data indicate that IUT has a number of advantages as compared with postnatal BMT. Future studies examining the fine specificity of immunoreconstitution in IUT versus postnatal BMT are indicated. (C) 1998 by The American Society of Hematology.