Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Amendment history:
  • Correction (October 1998)

Research Article Free access | 10.1172/JCI2723

Induction of insulitis by glutamic acid decarboxylase peptide-specific and HLA-DQ8-restricted CD4(+) T cells from human DQ transgenic mice.

L Wen, F S Wong, L Burkly, M Altieri, C Mamalaki, D Kioussis, R A Flavell, and R S Sherwin

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Wen, L. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Wong, F. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Burkly, L. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Altieri, M. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Mamalaki, C. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Kioussis, D. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Flavell, R. in: PubMed | Google Scholar

Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Sherwin, R. in: PubMed | Google Scholar

Published September 1, 1998 - More info

Published in Volume 102, Issue 5 on September 1, 1998
J Clin Invest. 1998;102(5):947–957. https://doi.org/10.1172/JCI2723.
© 1998 The American Society for Clinical Investigation
Published September 1, 1998 - Version history
View PDF
Abstract

Insulin-dependent diabetes mellitus in humans is linked with specific HLA class II genes, e.g., HLA-DQA1*0301/ DQB1*0302 (DQ8). To investigate the roles of HLA-DQ8 molecules and glutamic acid decarboxylase (GAD) in disease development, we generated DQ8(+)/I-Abo transgenic mice expressing functional HLA-DQ8 molecules and devoid of endogenous mouse class II. DQ8(+)/I-Abo mice produced antigen-specific antibodies and formed germinal centers after immunization with GAD65 peptides. Two GAD peptide-specific (247-266 and 509-528), DQ8 restricted Th1 CD4(+) T cell lines, were generated from immunized DQ8(+)/I-Abo mice. They induced severe insulitis after adoptive transfer into transgene positive (but not negative) mice who were treated with a very low dose of streptozotocin that alone caused no apparent islet pathology. In addition to CD4, islet mRNA from these mice also showed expression of CD8, IFNgamma, TNFalpha, Fas, and Fas ligand. Our data suggest that a mild islet insult in the presence of HLA-DQ8 bearing antigen-presenting cells promotes infiltration of GAD peptide reactive T cells into the islet.

Version history
  • Version 1 (September 1, 1998): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts