T-CELL-MEDIATED EXOCRINE PANCREATIC DAMAGE IN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-DEFICIENT MICE

Background & Aims: Recent observations suggest a role for lymphocytes in human pancreatitis. However, existing animal models of pancreatitis are not immunologically based. In studies on major histocompatibility complex (MHC) Il-deficient mice backcrossed five generations onto a C 57BL/6 background, we discovered a progressive wasting disease due to pancreatic damage. The purpose of this study was to characterize this model of immune-based pancreatic injury. Methods: The pathology was ch aracterized histologically and functionally by assaying for pancreatic enzymes and glucose. Results: By 6 months, a periductal lymphocytic i nfiltrate was observed that later developed into pancreatic lesions wi th extensive, but selective, destruction of acinar cells. Mice eventua lly lost weight, developed a hunched appearance, and began to pass lar ge, pale pellets. Histology of affected mice revealed pancreatic atrop hy with almost complete loss of acinar cells, although islets remained intact. Serum levels of amylase, lipase, and glucose confirmed the se lective loss of the exocrine pancreas, with both amylase and lipase le vels being significantly decreased in affected mice. However, glucose levels remained unaffected, Adoptive transfer of splenic mononuclear c ells to athymic mice was found to transfer the disease. Conclusions: A ged MHC II-deficient mice develop an immune-based pancreatitis with se lective loss of exocrine cells and function.