Reversal of Sjogren's-like syndrome in non-obese diabetic mice.
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.


CONCLUSIONS
This study establishes that a brief intervention in NOD mice with Sjögren's-like syndrome can reverse salivary gland dysfunction.
Tran
Simon D
SD
McGill University, 3640 University Street, M/43, Montreal, Quebec, Canada H3A 2B2. simon.tran@mcgill.ca
Kodama
Shohta
S
Lodde
Beatrijs M
BM
Szalayova
Ildiko
I
Key
Sharon
S
Khalili
Saeed
S
Faustman
Denise L
DL
Mezey
Eva
E
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012469:Salivary Glands / Q000503:physiopathology; D012472:Salivation; D012636:Secretory Rate; D012859:Sjogren's Syndrome / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013154:Spleen / Q000637:transplantation
D005620:Freund's Adjuvant