The Journal of Immunology, Vol 153, Issue 6 2769-2777, Copyright © 1994 by American Association of Immunologists

ARTICLES

A new animal model for primary Sjogren's syndrome in NFS/sld mutant mice

N Haneji, H Hamano, K Yanagi and Y Hayashi
Department of Pathology, Tokushima University School of Dentistry, Japan.

In this study, we report an established and characterized animal model for primary Sjogren's syndrome in NFS/sld mutant mice bearing an autosomal recessive gene with sublingual gland differentiation arrest. Significant inflammatory changes develop spontaneously in both the salivary and lacrimal glands of NFS/sld mutant mice thymectomized 3 days after 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 involves the parotid, submandibular salivary, and lacrimal glands. A significantly 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 inflammatory infiltration into the salivary and lacrimal glands consisted mainly of CD3+ and CD4+ T cells, and a lesser proportion of CD8+ T cells and B220+ B cells during the course of disease. When the repertoire of TCR V beta genes transcribed and expressed within the inflammatory infiltrates was analyzed in mice with autoimmune lesions, a considerable preferential use of TCR V beta gene (V beta 8 predominant) was detected in these lesions from the onset of disease. Thus, we can propose a newly established animal model for primary Sjogren's syndrome developing in this mutant strain of mice. Moreover, the predominant patterns of TCR transcript expression in an animal model may be somewhat restricted, suggesting that TCR-based immunotherapy of Sjogren's syndrome is possible.

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