Pancreatic IL-4 expression results in islet-reactive Th2 cells that inhibit diabetogenic lymphocytes in the nonobese diabetic mouse

W. Scott Gallichan, Balaji Balasa, Joanna D. Davies, Nora Sarvetnick

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Abstract

When immunological tolerance breaks down, autoimmune destruction of insulin-producing β cells in the pancreas can cause insulin-dependent diabetes mellitus. We previously showed that transgenic nonobese diabetic (NOD) mice expressing IL-4 in the pancreas (NOD-IL-4 mice) were protected from insulitis and diabetes. Here we have characterized the avoidance of pathological autoimmunity in these mice. The absence of disease did not result from a lack of T cell priming, because T cells responding to dominant islet Ags were present. These islet Ag-specific T cells displayed a Th2 phenotype, indicating that Th2 responses could account for the observed tolerance. Interestingly, islet Ag-specific Th1 T cells were present and found to be functional, because neutralization of the Th2 effector cytokines IL-4 and IL-10 resulted in diabetes. Histological examination revealed that NOD-IL-4 splenocytes inhibited diabetogenic T cells in cotransfer experiments by limiting insulitis and delaying diabetes. Neutralization of IL-4 in this system abrogated the ability of NOD-IL-4 splenocytes to delay the onset of diabetes. These results indicate that IL-4 expressed in the islets does not prevent the generation of pathogenic islet responses but induces islet Ag- specific Th2 T cells that block the action of diabetogenic T cells in the pancreas.

Original languageEnglish (US)
Pages (from-to)1696-1703
Number of pages8
JournalJournal of Immunology
Volume163
Issue number3
StatePublished - Aug 1 1999

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Th2 Cells
Inbred NOD Mouse
Interleukin-4
Lymphocytes
T-Lymphocytes
Pancreas
Th1 Cells
Autoimmunity
Type 1 Diabetes Mellitus
Interleukin-10
Transgenic Mice
Insulin
Cytokines
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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Pancreatic IL-4 expression results in islet-reactive Th2 cells that inhibit diabetogenic lymphocytes in the nonobese diabetic mouse. / Gallichan, W. Scott; Balasa, Balaji; Davies, Joanna D.; Sarvetnick, Nora.

In: Journal of Immunology, Vol. 163, No. 3, 01.08.1999, p. 1696-1703.

Research output: Contribution to journalArticle

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