Failure of alpha-galactosylceramide to prevent diabetes in virus-inducible models of type 1 diabetes in the rat
Authors
Chopra, PrernaDiiorio, Philip J.
Pino, Steven C.
Wilson, S. Brian
Phillips, Nancy E.
Mordes, John P.
Rossini, Aldo A.
Greiner, Dale L.
Shultz, Leonard D.
Bortell, Rita
UMass Chan Affiliations
Department of Medicine, Division of Endocrinology and MetabolismDepartment of Medicine, Division of Diabetes
Document Type
Journal ArticlePublication Date
2009-05-06Keywords
AnimalsCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Diabetes Mellitus, Type 1
Disease Models, Animal
Female
Galactosylceramides
Interferon-gamma
Interleukin-12
Interleukin-4
Male
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Rats
Sex Factors
Spleen
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
BACKGROUND: Alpha-galactosylceramide (alpha-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in human diabetes. MATERIALS AND METHODS: To evaluate this therapeutic issue further, BBDR and LEW.1WR1 rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes. RESULTS: alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFNgamma in all rat strains, but less than mouse splenocytes. Rat splenocytes stimulated with alpha-GalCer preferentially produced IL-12, whereas mouse splenocytes preferentially produced IL-4. CONCLUSION: alpha-GalCer elicits species-specific cytokine responses in iNKT cells. In humans with type 1 diabetes, differences in iNKT cell responses to stimulation with alpha-GalCer due to age, genetic variability and other factors may influence its therapeutic potential.Source
In Vivo. 2009 Mar-Apr;23(2):195-201.