Combined treatment with CD40 costimulation blockade, T-cell depletion, low-dose irradiation, and donor bone marrow transfusion in limb allograft survival.
Combined treatment with CD40 costimulation blockade, T-cell depletion, low-dose irradiation, and donor bone marrow transfusion in limb allograft survival.
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联合治疗 CD40 共刺激阻断、T 细胞耗竭、低剂量照射和供体骨髓输注对肢体同种异体移植存活的影响。
DOI：
10.1097/01.sap.0000182651.68061.5a
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发表时间：
2005
影响因子：
1.5
通讯作者：
Mohanakumar,T
中科院分区：
文献类型：
--
作者：
Tung,ThomasH;Mackinnon,SusanE;Mohanakumar,T
为了确定基于CD 40共刺激阻断和供体骨髓的方案在肢体同种异体移植物模型中的功效，C57 Bl/6小鼠接受来自Balb/c小鼠的肢体同种异体移植物，并且不进行处理或结合MR 1（抗CD 40配体单克隆抗体）、CD 4+和CD 8 + T细胞消耗抗体、低剂量照射和来自Balb/c供体的骨髓输注1或2周。接受1周治疗的受者在38.2±5.4（平均值±SEM）天出现排斥反应，而接受2周治疗的受者的同种异体移植物存活率为56.5±9.9，最长可达91天。组织学显示排斥反应较少细胞介导，提示移植血管病变。首先发生皮肤的差异性排斥反应。因此，基于CD 40共刺激阻断和供体骨髓的联合方案显著延长了同种异体移植物存活。然而，没有达到耐受性，组织学提示慢性排斥反应可能是同种异体移植物丢失的原因。
To determine the efficacy of a regimen based on CD40 costimulation blockade and donor bone marrow in the limb allograft model, C57Bl/6 mice received limb allografts from Balb/c mice and either no treatment or a combination of MR1 (anti-CD40 ligand monoclonal antibody), CD4+ and CD8+ T-cell-depleting antibodies, low-dose irradiation, and bone marrow transfusion from Balb/c donors for 1 or 2 weeks. Recipients treated for 1 week showed rejection at 38.2±5.4 (mean±SEM) days, while those treated for 2 weeks had allograft survival of 56.5±9.9, with a range up to 91 days. Histology demonstrated rejection which was less cell-mediated and suggestive of transplant vasculopathy. Differential rejection of skin occurred first. Thus, a combined regimen based on CD40 costimulatory blockade and donor marrow significantly prolonged allograft survival. However, tolerance was not achieved, and histology suggests chronic rejection as a possible cause of allograft loss.