Details

Autor(en) / Beteiligte

• King, Marie
• Pearson, Todd
• Shultz, Leonard D
• Leif, Jean
• 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
• Greiner, Dale L

Titel

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

Ist Teil von

• Clinical immunology (Orlando, Fla.), 2008-03, Vol.126 (3), p.303-314

Ort / Verlag

San Diego, CA: Elsevier Inc

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Immunodeficient NOD- scid mice bearing a targeted mutation in the IL2 receptor common gamma chain ( Il2rγ null ) readily engraft with human stem cells. Here we analyzed human peripheral blood mononuclear cells (PBMC) for their ability to engraft NOD- scid Il2rγ null mice and established engraftment kinetics, optimal cell dose, and the influence of injection route. Even at low PBMC input, NOD- scid Il2rγ 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 Il2rγ 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 Il2rγ null mice may represent an important surrogate for investigating in vivo mechanisms of human islet allograft rejection.