Abstract

Objective: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjögren’s-like syndrome. We tested if a therapy that reverses end-stage diabetes in the NOD mouse would affect their Sjögren’s-like syndrome.

Methods: NOD mice have a proteasome defect. Improperly selected naïve T cells escape but can be killed by re-introducing MHC class I-self peptides on matched normal splenocytes. The proteasome defect also impairs NFkB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to TNF induced apoptosis stimulated via complete Freund’s adjuvant (CFA). We studied the impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice.

Results: All NOD mice receiving the above therapy had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be a result of a combination of rescue and regeneration of the gland, as confirmed with immunohistochemistry. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycemia and death.

Conclusion: This study establishes that a brief intervention into NOD mice with Sjögren’s-like syndrome can reverse salivary gland dysfunction.