Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse

Fu Dong Shi, Malin Flodström, Balaji Balasa, Soon Ha Kim, Kurt Van Gunst, Jack L. Strominger, S. Brian Wilson, Nora Sarvetnick

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Abstract

Quantitative and qualitative defects in CD1-restricted natural killer T cells have been reported in several autoimmune-prone strains of mice, including the nonobese diabetic (NOD) mouse. These defects are believed to be associated with the emergence of spontaneous autoimmunity. Here we demonstrate that both CD1d-null NOD and CD1d-null NOD/BDC2.5 T cell receptor transgenic mice have an accelerated onset and increased incidence of diabetes when compared with CD1d+/- and CD1d+/+ littermates. The acceleration of disease did not seem to result from changes in the T helper (Th)1/Th2 balance because lymphocytes purified from lymphoid organs and pancreatic islets of wild-type and CD1d-null mice secreted equivalent amounts of IFN-γ and IL-4 after stimulation. In contrast, the pancreata of CD1d-null mice harbored significantly higher numbers of activated memory T cells expressing the chemokine receptor CCR4. Notably, the presence of these T cells was associated with immunohistochemical evidence of increased destructive insulitis. Thus, CD1d-restricted T cells are critically important for regulation of the spontaneous disease process in NOD mice.

Original languageEnglish (US)
Pages (from-to)6777-6782
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number12
DOIs
StatePublished - Jun 5 2001

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Inbred NOD Mouse
Germ Cells
T-Lymphocytes
Natural Killer T-Cells
Chemokine Receptors
T-Cell Antigen Receptor
Autoimmunity
Islets of Langerhans
Interleukin-4
Transgenic Mice
Pancreas
Lymphocytes
Incidence

ASJC Scopus subject areas

  • General

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Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. / Shi, Fu Dong; Flodström, Malin; Balasa, Balaji; Kim, Soon Ha; Van Gunst, Kurt; Strominger, Jack L.; Wilson, S. Brian; Sarvetnick, Nora.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 12, 05.06.2001, p. 6777-6782.

Research output: Contribution to journalArticle

Shi, Fu Dong ; Flodström, Malin ; Balasa, Balaji ; Kim, Soon Ha ; Van Gunst, Kurt ; Strominger, Jack L. ; Wilson, S. Brian ; Sarvetnick, Nora. / Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 12. pp. 6777-6782.
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