Th1 and Th2 pancreatic inflammation differentially affects homing of islet-reactive CD4 cells in nonobese diabetic mice

Natasha J. Hill, Kurt Van Gunst, Nora Sarvetnick

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The control of lymphocyte recruitment to the site of inflammation is an important component determining the pathogenicity of an autoimmune response. Progression from insulitis to diabetes in the nonobese diabetic mouse is typically associated with Th1 pancreatic inflammation, whereas Th2 inflammation can seemingly be controlled indefinitely. We show that a Th1 (IFN-γ) pancreatic environment greatly accelerates the recruitment of adoptively transferred islet-specific CD4 T cells to the islets and also accelerates the onset of diabetes. The increased number of islet-reactive T cells in the pancreas does not result from increased proliferation or a decreased rate of apoptosis; instead, it appears to be caused by a greatly facilitated rate of entry to the pancreas. In contrast, a Th2 (IL-4) pancreatic environment does act to enhance Ag-specific proliferation and decrease the rate of apoptosis in islet-specific CD4 T cells. Nonpathogenic/regulatory cells are not preferentially expanded by the presence of IL-4. Increased recruitment to the islets was also observed in the presence of IL-4, but to a lesser extent than in the presence of IFN-γ, and this lesser increase in the rate of recruitment did not accelerate diabetes onset within the time period examined. Therefore, the production of Th1 cytokines by initial islet-infiltrating cells may cause a greater increase than Th2 cytokines in the rate of recruitment of activated T cells. This difference in rate of recruitment may be critical in determining whether the initial infiltrate proceeds to diabetes or whether a steady state insulitis develops that can be maintained.

Original languageEnglish (US)
Pages (from-to)1649-1658
Number of pages10
JournalJournal of Immunology
Issue number4
StatePublished - Feb 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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