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
Department of Medicine, Division of Diabetes; Department of Pathology; Department of Molecular Genetics and Microbiology; Department of Physiology
Medical Subject Headings
Animals; Diabetes Mellitus; Disease Models, Animal; Graft Rejection; Humans; Interleukin Receptor Common gamma Subunit; Islets of Langerhans; Islets of Langerhans Transplantation; Leukocytes, Mononuclear; Mice; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Mutation; Phenotype
Allergy and Immunology | Endocrinology, Diabetes, and Metabolism | Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
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Citation: Clin Immunol. 2008 Mar;126(3):303-14. Epub 2007 Dec 21. Link to article on publisher's site
King, Marie A.; Pearson, Todd; Shultz, Leonard D.; Leif, Jean H.; Bottino, Rita; Trucco, Massimo; Atkinson, Mark A.; Wasserfall, Clive; Herold, Kevan C.; Woodland, Robert T.; Schmidt, Madelyn R.; Woda, Bruce A.; Thompson, Michael J.; Rossini, Aldo A.; and Greiner, Dale L., "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" (2007). GSBS Student Publications. Paper 352.