Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II

Yogish C Kudva, Govindarajan Rajagopalan, Raghavan Raju, Roshini S. Abraham, Michelle Smart, Julie Hanson, Chella S. David

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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-Ag7 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-Ag7 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-Ag7+/+ mice revealed significant intra-islet infiltration. Although a characteristic peri-insulitis/peri-ductulitis was present in Aβ0/NOD mice, islets from DR3, DQ8 and DR3.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.

Original languageEnglish (US)
Pages (from-to)987-999
Number of pages13
JournalHuman Immunology
Volume63
Issue number11
DOIs
StatePublished - Nov 1 2002

Fingerprint

Inbred NOD Mouse
HLA Antigens
Type 1 Diabetes Mellitus
Cyclophosphamide
Transgenic Mice
Streptozocin
Incidence

Keywords

  • Diabetes
  • HLA-DQ8
  • HLA-DR3
  • Insulitis
  • Transgenes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II. / Kudva, Yogish C; Rajagopalan, Govindarajan; Raju, Raghavan; Abraham, Roshini S.; Smart, Michelle; Hanson, Julie; David, Chella S.

In: Human Immunology, Vol. 63, No. 11, 01.11.2002, p. 987-999.

Research output: Contribution to journalArticle

Kudva, Yogish C ; Rajagopalan, Govindarajan ; Raju, Raghavan ; Abraham, Roshini S. ; Smart, Michelle ; Hanson, Julie ; David, Chella S. / Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II. In: Human Immunology. 2002 ; Vol. 63, No. 11. pp. 987-999.
@article{551fc9e5ede644faa841e7441ae99466,
title = "Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II",
abstract = "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-Ag7 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-Ag7 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-Ag7+/+ mice revealed significant intra-islet infiltration. Although a characteristic peri-insulitis/peri-ductulitis was present in Aβ0/NOD mice, islets from DR3, DQ8 and DR3.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.",
keywords = "Diabetes, HLA-DQ8, HLA-DR3, Insulitis, Transgenes",
author = "Kudva, {Yogish C} and Govindarajan Rajagopalan and Raghavan Raju and Abraham, {Roshini S.} and Michelle Smart and Julie Hanson and David, {Chella S.}",
year = "2002",
month = "11",
day = "1",
doi = "10.1016/S0198-8859(02)00435-4",
language = "English (US)",
volume = "63",
pages = "987--999",
journal = "Human Immunology",
issn = "0198-8859",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II

AU - Kudva, Yogish C

AU - Rajagopalan, Govindarajan

AU - Raju, Raghavan

AU - Abraham, Roshini S.

AU - Smart, Michelle

AU - Hanson, Julie

AU - David, Chella S.

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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-Ag7 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-Ag7 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-Ag7+/+ mice revealed significant intra-islet infiltration. Although a characteristic peri-insulitis/peri-ductulitis was present in Aβ0/NOD mice, islets from DR3, DQ8 and DR3.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.

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-Ag7 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-Ag7 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-Ag7+/+ mice revealed significant intra-islet infiltration. Although a characteristic peri-insulitis/peri-ductulitis was present in Aβ0/NOD mice, islets from DR3, DQ8 and DR3.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.

KW - Diabetes

KW - HLA-DQ8

KW - HLA-DR3

KW - Insulitis

KW - Transgenes

UR - http://www.scopus.com/inward/record.url?scp=0036828265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036828265&partnerID=8YFLogxK

U2 - 10.1016/S0198-8859(02)00435-4

DO - 10.1016/S0198-8859(02)00435-4

M3 - Article

C2 - 12392851

AN - SCOPUS:0036828265

VL - 63

SP - 987

EP - 999

JO - Human Immunology

JF - Human Immunology

SN - 0198-8859

IS - 11

ER -