Autoimmune pancreatitis in MRL/Mp mice is a T cell-mediated disease responsive to cyclosporine A and rapamycin treatment

摘要: Background Autoimmune pancreatitis (AIP) in humans invariably responds to steroid treatment, but little is known about the underlying pathogenesis and benefits of alternative treatments. Objective To study pathogenesis, efficacy immunosuppressant agents MRL/Mp mouse model AIP. Design mice were pretreated for 4 weeks with polyinosinic:polycytidylic acid induce Pancreatic sections genetically deleted CTLA-4 analysed. Blockage was achieved by intraperitoneal antibody treatment 2 μg/g anti-mouse-CD152. Subsequent therapeutic studies performed a period using cyclosporine A (40 μg/g), rapamycin (1 μg/g) or azathioprine (15 μg/g). Results suppressed regulatory T cell (Treg) function raised effector (Teff) response subsequent histomorphological organ destruction, indicating that AIP cell-driven disease. Using an established histopathological score, we found dexamethasone, rapamycin, less so azathioprine, reduced pancreatic damage. However, beneficial effects via different mechanisms: inhibited Teff activation proliferation whereas led selective expansion Tregs which subsequently response. Conclusions The calcineurin inhibitor mammalian target (mTOR) inhibitor, improve course mechanisms. These findings further support concept autoreactive cells as key players suggest should be considered humans.