Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice

Craig Meagher, Qizhi Tang, Brian T. Fife, Helene Bour-Jordan, Jenny Wu, Cecile Pardoux, Mingying Bi, Kristin Melli, Jeffrey A. Bluestone

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Autoimmune pancreatitis (AIP) is a heterogeneous autoimmune disease in humans characterized by a progressive lymphocytic and plasmacytic infiltrate in the exocrine pancreas. In this study, we report that regulatory T cell-deficient NOD.CD28KO mice spontaneously develop AIP that closely resembles the human disease. NOD mouse AIP was associated with severe periductal and parenchymal inflammation of the exocrine pancreas by CD4+ T cells, CD8 + T cells, and B cells. Spleen CD4+ T cells were found to be both necessary and sufficient for the development of AIP. Autoantibodies and autoreactive T cells from affected mice recognized a ∼50-kDa protein identified as pancreatic amylase. Importantly, administration of tolerogenic amylase-coupled fixed spleen cells significantly ameliorated disease severity, suggesting that this protein functions as a key autoantigen. The establishment and characterization of this spontaneous pancreatic amylase-specific AIP in regulatory T cell-deficient NOD.CD28KO mice provides an excellent model for the study of disease pathogenesis and development of new therapies for human autoimmune pancreatitis.

Original languageEnglish (US)
Pages (from-to)7793-7803
Number of pages11
JournalJournal of Immunology
Volume180
Issue number12
DOIs
StatePublished - 2008

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