A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene
A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene
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DOI：
10.1016/j.clim.2007.11.001
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发表时间：
2008-03-01
影响因子：
8.6
通讯作者：
Greiner, Date L.
中科院分区：
文献类型：
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作者：
King, Marie;Pearson, Todd;Greiner, Date L.
免疫缺陷的NOD-SCID小鼠在IL2受体共同伽马链(IL2R(NULL))中携带靶向突变，很容易与人类干细胞移植。在这里，我们分析了人外周血单个核细胞(PBMC)植入Nod-SCID Il2r(NULL)小鼠的能力，并建立了植入动力学、最佳细胞剂量和注射途径的影响。即使在低PBMC输入下，NOD-SCID Il2r(空)小鼠也能在3-4周内重复支持高水平的人PBMC植入。与以前的免疫缺陷小鼠相比，我们观察到供体内和供体间植入的低变异性。经链脲佐菌素治疗后血糖升高的NOD-SCID Il2r(Null)小鼠在与人胰岛移植后恢复正常血糖。有趣的是，这些人胰岛移植物在注射了人类白细胞抗原不相合的人PBMC后被排斥，表现为回到高血糖和人C肽的翻转。这些数据表明，人源化NOD-SCID Il2r(Null)小鼠可能是研究人同种异体胰岛移植排斥反应的体内机制的重要替代物。(C)2007 Elsevier Inc.保留所有权利。
Immunodeficient NOD-scid mice bearing a targeted mutation in the IL2 receptor common gamma chain (Il2r gamma(null)) readily engraft with human stem cells. Here we analyzed human peripheral blood mononuclear cells (PBMC) for their ability to engraft NOD-scid Il2r gamma(null) mice and established engraftment kinetics, optimal cell dose, and the influence of injection route. Even at low PBMC input, NOD-scid Il2r gamma(null) mice reproducibly support high human PBMC engraftment that plateaus within 3 - 4 weeks. In contrast to previous stocks of immunodeficient mice, we observed low intra- and inter-donor variability of engraftment. NOD-scid Il2r gamma(null) mice rendered hyperglycemic by streptozotocin treatment return to normoglycemia following transplantation with human islets. Interestingly, these human islet grafts are rejected following injection of HLA-mismatched human PBMC, as evidenced by return to hyperglycemia and toss of human C-peptide. These data suggest that humanized NOD-scid Il2r gamma(null) mice may represent an important surrogate for investigating in vivo mechanisms of human islet allograft rejection. (c) 2007 Elsevier Inc. All rights reserved.