PMID- 18096436
OWN - NLM
STAT- MEDLINE
DCOM- 20080402
LR  - 20080218
IS  - 1521-6616 (Print)
IS  - 1521-6616 (Linking)
VI  - 126
IP  - 3
DP  - 2008 Mar
TI  - 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.
PG  - 303-14
AB  - 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.
FAU - King, Marie
AU  - King M
AD  - Department of Medicine, University of Massachusetts Medical School, 373 
      Plantation Street, Worcester, MA 01655, USA.
FAU - Pearson, Todd
AU  - Pearson T
FAU - Shultz, Leonard D
AU  - Shultz LD
FAU - Leif, Jean
AU  - Leif J
FAU - Bottino, Rita
AU  - Bottino R
FAU - Trucco, Massimo
AU  - Trucco M
FAU - Atkinson, Mark A
AU  - Atkinson MA
FAU - Wasserfall, Clive
AU  - Wasserfall C
FAU - Herold, Kevan C
AU  - Herold KC
FAU - Woodland, Robert T
AU  - Woodland RT
FAU - Schmidt, Madelyn R
AU  - Schmidt MR
FAU - Woda, Bruce A
AU  - Woda BA
FAU - Thompson, Michael J
AU  - Thompson MJ
FAU - Rossini, Aldo A
AU  - Rossini AA
FAU - Greiner, Dale L
AU  - Greiner DL
LA  - eng
GR  - AI 041054/AI/NIAID NIH HHS/United States
GR  - AI 17672/AI/NIAID NIH HHS/United States
GR  - AI 42288/AI/NIAID NIH HHS/United States
GR  - AI 46629/AI/NIAID NIH HHS/United States
GR  - AI 51405/AI/NIAID NIH HHS/United States
GR  - AI 57463/AI/NIAID NIH HHS/United States
GR  - CA 34196/CA/NCI NIH HHS/United States
GR  - DK 32520/DK/NIDDK NIH HHS/United States
GR  - DK 53006/DK/NIDDK NIH HHS/United States
GR  - DK 57846/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071221
PL  - United States
TA  - Clin Immunol
JT  - Clinical immunology (Orlando, Fla.)
JID - 100883537
RN  - 0 (Interleukin Receptor Common gamma Subunit)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus/immunology
MH  - Disease Models, Animal
MH  - Graft Rejection/immunology
MH  - Humans
MH  - Interleukin Receptor Common gamma Subunit/*deficiency/*genetics
MH  - Islets of Langerhans/*immunology
MH  - Islets of Langerhans Transplantation/immunology
MH  - Leukocytes, Mononuclear/*immunology/transplantation
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - Mutation/*genetics
MH  - Phenotype
EDAT- 2007/12/22 09:00
MHDA- 2008/04/03 09:00
CRDT- 2007/12/22 09:00
PHST- 2007/07/20 00:00 [received]
PHST- 2007/11/07 00:00 [revised]
PHST- 2007/11/12 00:00 [accepted]
PHST- 2007/12/22 09:00 [pubmed]
PHST- 2008/04/03 09:00 [medline]
PHST- 2007/12/22 09:00 [entrez]
AID - S1521-6616(07)01405-2 [pii]
AID - 10.1016/j.clim.2007.11.001 [doi]
PST - ppublish
SO  - Clin Immunol. 2008 Mar;126(3):303-14. doi: 10.1016/j.clim.2007.11.001. Epub 2007 
      Dec 21.