[Investigations of various animal models for Sjögren's syndrome]

Several animal models for studying immune-mediated sialadenitis include autoimmune-prone mice which develop lesions spontaneously, and non-autoimmune-prone mice in which the lesions can be induced by various experimental manipulations. Autoimmune disease-prone mice such as NZB, NZB/WF1, MRL/lpr, SL/Ni, and NOD (non-obese diabetic) have been used as animal models for the investigation of Sjögren's syndrome in humans. We have previously demonstrated murine experimental systems in which autoimmune sialadenitis was induced in several strains of thymectomized mice, and developed spontaneously in certain strains of aged mice with H-2 restriction. We have recently established an animal model for primary Sjögren's syndrome in NFS/sld mutant mice bearing an autosomal recessive gene with sublingual gland differentiation arrest. A significantly higher incidence of autoimmune lesions in the salivary and lacrimal gland was found in female mice, and the anti-salivary duct autoantibodies were detected in sera from mice with autoimmune lesions. A preferential use of TCRV beta gene was detected in autoimmune lesions from the onset of disease, suggesting that TCR-based immunotherapy is possible.