NEW ANIMAL-MODEL FOR PRIMARY SJOGRENS-SYNDROME IN NFS SLD MUTANT MICE/

In this study, we report an established and characterized animal model for primary Sjogren's syndrome in NFS/sld mutant mice bearing an auto somal recessive gene with sublingual gland differentiation arrest. Sig nificant inflammatory changes develop spontaneously in both the saliva ry and lacrimal glands of NFS/sld mutant mice thymectomized 3 days aft er birth without any immunization, whereas no significant inflammatory lesions were found in other organs or in nonthymectomized mice. This pathology resembles primary Sjogren's syndrome in humans, which involv es the parotid, submandibular salivary, and lacrimal glands. A signifi cantly higher incidence of autoimmune lesions was found in female mice , and the anti-salivary duct autoantibodies were detected in sera from mice with autoimmune lesions but not in control mice. The inflammator y infiltration into the salivary and lacrimal glands consisted mainly of CD3(+) and CD4(+) T cells, and a lesser proportion of CD8(+) T cell s and B220(+) B cells during the course of disease. When the repertoir e of TCR V beta genes transcribed and expressed within the inflammator y infiltrates was analyzed in mice with autoimmune lesions, a consider able preferential use of TCR V beta gene (V beta 8 predominant) was de tected in these lesions from the onset of disease. Thus, we can propos e a newly established animal model for primary Sjogren's syndrome deve loping in this mutant strain of mice. Moreover, the predominant patter ns of TCR transcript expression in an animal model may be somewhat res tricted, suggesting that TCR-based immunotherapy of Sjogren's syndrome is possible.