TY - JOUR
T1 - Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice
AU - Meagher, Craig
AU - Tang, Qizhi
AU - Fife, Brian T.
AU - Bour-Jordan, Helene
AU - Wu, Jenny
AU - Pardoux, Cecile
AU - Bi, Mingying
AU - Melli, Kristin
AU - Bluestone, Jeffrey A.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.180.12.7793
DO - 10.4049/jimmunol.180.12.7793
M3 - Article
C2 - 18523243
AN - SCOPUS:50949119996
SN - 0022-1767
VL - 180
SP - 7793
EP - 7803
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -