PMID- 12392851
OWN - NLM
STAT- MEDLINE
DCOM- 20030411
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 63
IP  - 11
DP  - 2002 Nov
TI  - Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD 
      mice lacking endogenous MHC class II.
PG  - 987-99
AB  - To evaluate the contributions of DR3 and DQ8 to the etiopathogenesis of type 1 
      diabetes in a diabetes-predisposing milieu, we developed human leukocyte antigen 
      (HLA) transgenic mice on the nonobese diabetic (NOD) background in the absence of 
      the endogenous class II molecule, I-A(g7) and studied the incidence of both 
      spontaneous and experimental (induced) autoimmune diabetes. Transgenic expression 
      of HLA-DR3 and -DQ8 (either alone or in combination) did not confer 
      susceptibility to spontaneous or cyclophosphamide-induced type 1 diabetes. 
      Expression of I-A(g7) was mandatory for development of spontaneous or 
      cyclophosphamide-induced diabetes. However, multiple low doses of streptozotocin 
      could induce diabetes in all groups of mice independent of the class II molecules 
      expressed. In unmanipulated mice, only islets from I-A(g7+/+) mice revealed 
      significant intra-islet infiltration. Although a characteristic 
      peri-insulitis/peri-ductulitis was present in Abeta(0)/NOD mice, islets from DR3, 
      DQ8 and DR3 x DQ8 double transgenic mice demonstrated significantly less 
      infiltration. In conclusion, transgenic expression of HLA-DR3 and -DQ8 associated 
      with predisposition to type 1 diabetes alone is not sufficient to induce 
      spontaneous diabetes in NOD mice lacking endogenous class II molecules.
FAU - Kudva, Yogish C
AU  - Kudva YC
AD  - Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA.
FAU - Rajagopalan, Govindarajan
AU  - Rajagopalan G
FAU - Raju, Raghavan
AU  - Raju R
FAU - Abraham, Roshini S
AU  - Abraham RS
FAU - Smart, Michelle
AU  - Smart M
FAU - Hanson, Julie
AU  - Hanson J
FAU - David, Chella S
AU  - David CS
LA  - eng
GR  - AI-14764/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (CD4 Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 5W494URQ81 (Streptozocin)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Animals
MH  - CD4 Antigens/physiology
MH  - Cyclophosphamide/pharmacology
MH  - Diabetes Mellitus, Type 1/*etiology/immunology/pathology
MH  - Female
MH  - Glucose Tolerance Test
MH  - HLA-DQ Antigens/*physiology
MH  - HLA-DR3 Antigen/*physiology
MH  - Inflammation/etiology
MH  - Islets of Langerhans/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell, alpha-beta/analysis
MH  - Salivary Glands/pathology
MH  - Streptozocin
MH  - T-Lymphocytes/physiology
EDAT- 2002/10/24 04:00
MHDA- 2003/04/12 05:00
CRDT- 2002/10/24 04:00
PHST- 2002/10/24 04:00 [pubmed]
PHST- 2003/04/12 05:00 [medline]
PHST- 2002/10/24 04:00 [entrez]
AID - S0198885902004354 [pii]
AID - 10.1016/s0198-8859(02)00435-4 [doi]
PST - ppublish
SO  - Hum Immunol. 2002 Nov;63(11):987-99. doi: 10.1016/s0198-8859(02)00435-4.