| Autor: |
Meagher, Craig, Tang, Qizhi, Fife, Brian T., Bour-Jordan, Helene, Wu, Jenny, Pardoux, Cecile, Bi, Mingying, Melli, Kristin, Bluestone, Jeffrey A. |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
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| Popis: |
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 approximately 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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