Autoantibodies in Salivary Hypofunction in the NOD Mousea,

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Abstract
The nonobese diabetic (NOD) mouse exhibits spontaneous salivary gland infiltration and loss of salivary function independent of its propensity to develop diabetes, and thus can serve as a model for salivary hypofunction in Sjögren's syndrome (SS). Studies by others have indicated that this pathology depends on lymphocytes and thus may be autoimmune mediated. We have found that NOD mice four months of age and older exhibit a 90-95% reduction in pilocarpine-stimulated salivary flow (5.8 +/- 6.6 mg/5 min) as compared to age- and sex-matched C57B1/10 controls (98.4 +/- 52.3 mg/5 min). These mice simultaneously possess only sparse mononuclear cell infiltrates (averaging approximately one small and one large focus per whole-gland section) in the submandibular glands, suggesting that loss of salivary function does not require massive infiltration of the salivary glands. NOD serum autoantibodies to salivary gland proteins are demonstrable by Western blotting, and, as in a subset of SS patients, some NOD serum autoantibodies recognize neural antigens. Splenic T-cell reactivity to salivary and neural proteins can also be observed. Transfer experiments using NOD mouse serum suggest that loss of salivary function, evaluated as a decrease in pilocarpine-stimulated flow rate, can be transferred by humoral factors, possibly autoantibodies. These results suggest that autoimmune mechanisms dependent on both autoantibody and autoreactive T cells can mediate loss of salivary function, and that salivary and/or neural antigens may serve as a target for these autoimmune reactions.