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Reversal of Sjögren’s-like syndrome in non-obese diabetic mice
  1. Simon D Tran1,*,
  2. Shohta Kodama2,*,
  3. Beatrijs M Lodde4,
  4. Ildiko Szalayova4,
  5. Sharon Key4,
  6. Saeed Khalili1,
  7. Denise L Faustman3,
  8. Éva Mezey4
  1. 1McGill University, Montreal, Quebec, Canada
  2. 2Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  3. 3Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  4. 4National Institutes of Health, NIDCR, CSDB, Bethesda, Maryland, USA
  1. Correspondence to:
    Dr S D Tran
    McGill University, 3640 University Street, M/43, Montreal, Quebec, Canada H3A 2B2; simon.tran{at} and Dr E. Mezey; mezeye{at}


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

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