首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >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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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.

机译:一种新的Hu-PBL模型,用于研究人胰岛的同种异体反应性,该模型基于在IL-2受体γ链基因中靶向突变的NOD短尾小鼠。

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摘要

Immunodeficient NOD-scid mice bearing a targeted mutation in the IL2 receptor common gamma chain (Il2rgamma(null)) readily engraft with human stem cells. Here we analyzed human peripheral blood mononuclear cells (PBMC) for their ability to engraft NOD-scid Il2rgamma(null) mice and established engraftment kinetics, optimal cell dose, and the influence of injection route. Even at low PBMC input, NOD-scid Il2rgamma(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 Il2rgamma(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 loss of human C-peptide. These data suggest that humanized NOD-scid Il2rgamma(null) mice may represent an important surrogate for investigating in vivo mechanisms of human islet allograft rejection.
机译:免疫缺陷的NOD-scid小鼠在IL2受体共同的γ链(Il2rgamma(null))中具有定向突变,很容易植入人干细胞。在这里,我们分析了人类外周血单个核细胞(PBMC)植入NOD scIIl2rgamma(null)小鼠的能力,并建立了植入动力学,最佳细胞剂量以及注射途径的影响。即使在低PBMC输入下,NOD-scid Il2rgamma(null)小鼠也可再现地支持在3-4周内达到稳定水平的高人PBMC植入。与以前的免疫缺陷小鼠库存相反,我们观察到植入体内供体间和供体间的低变异性。用人胰岛移植后,通过链脲佐菌素治疗导致高血糖的NOD异常Il2rgamma(null)小鼠恢复正常血糖。有趣的是,这些人胰岛移植物在注射HLA不匹配的人PBMC后被排斥,这由高血糖症的恢复和人C肽的丢失所证明。这些数据表明,人源化的NOD-scid Il2rgamma(null)小鼠可能代表了研究人胰岛异体移植排斥反应体内机制的重要替代指标。

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