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In Vivo. 2009 Mar-Apr;23(2):195-201.

Failure of alpha-galactosylceramide to prevent diabetes in virus-inducible models of type 1 diabetes in the rat.

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  • 1Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

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.

PMID:
19414403
[PubMed - indexed for MEDLINE]
PMCID:
PMC2718559
Free PMC Article

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