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Åke Lernmark

Principal investigator

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Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

Author

  • John A Gebe
  • Kellee A Unrath
  • Ben A Falk
  • Ito Kouichi
  • Li Wen
  • Terri L Daniels
  • Åke Lernmark
  • Gerald T Nepom

Summary, in English

We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice

Department/s

  • Diabetes and Celiac Unit

Publishing year

2006

Language

English

Pages

294-304

Publication/Series

Clinical Immunology

Volume

121

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Immunology in the medical area

Keywords

  • Diabetes
  • Tolerance
  • MHC
  • T cells
  • Transgenic

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1521-6616