Reversal of Sjögren’s-like syndrome in non-obese diabetic mice
- Simon D Tran1,*,
- Shohta Kodama2,*,
- Beatrijs M Lodde4,
- Ildiko Szalayova4,
- Sharon Key4,
- Saeed Khalili1,
- Denise L Faustman3,
- Éva Mezey4
- 1McGill University, Montreal, Quebec, Canada
- 2Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- 3Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- 4National Institutes of Health, NIDCR, CSDB, Bethesda, Maryland, USA
- Correspondence to:
Dr S D Tran
McGill University, 3640 University Street, M/43, Montreal, Quebec, Canada H3A 2B2; and Dr E. Mezey; .
- Accepted 10 December 2006
- Published Online First 19 December 2006
Background: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjögren’s-like syndrome.
Objective: To test whether a treatment 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 naive T cells escape, but can be killed by reintroducing major histocompatibility complex class I self-peptides on matched normal splenocytes. The proteasome defect also impairs nuclear factor kB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to tumour necrosis factor-induced apoptosis stimulated through complete Freund’s adjuvant (CFA). The impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice was studied.
Results: All NOD mice receiving the above treatment had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be the result of a combination of rescue and regeneration of the gland, as confirmed by immunohistochemical analysis. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycaemia and death.
Conclusion: This study establishes that a brief intervention in NOD mice with Sjögren’s-like syndrome can reverse salivary gland dysfunction.
- CFA, complete Freund’s adjuvant
- FISH, fluorescence in situ hybridisation
- LMP, latent membrane protein
- MHC, major histocompatibility complex
- NFκB, nuclear factor κB
- NOD, non-obese diabetic
- SFR, salivary flow rate
- TNF, tumour necrosis factor
↵* These authors contributed equally to the work.
Published Online First 19 December 2006
Competing interests: None.