| First Author | Meagher C | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 12 | Pages | 7793-803 |
| PubMed ID | 18523243 | Mgi Jnum | J:137030 |
| Mgi Id | MGI:3797668 | Doi | 10.4049/jimmunol.180.12.7793 |
| Citation | Meagher C, et al. (2008) Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice. J Immunol 180(12):7793-803 |
| abstractText | 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. |
