Abstract
Background: α-Galactosylceramide (α-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, α-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 α-GalCer, and followed for onset of diabetes. Results: α-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with α-GalCer produced similar levels of IFNγ in all rat strains, but less than mouse splenocytes. Rat splenocytes stimulated with α-GalCer preferentially produced IL-12, whereas mouse splenocytes preferentially produced IL-4. Conclusion: α-GalCer elicits species-specific cytokine responses in iNKT cells. In humans with type 1 diabetes, differences in iNKT cell responses to stimulation with α-GalCer due to age, genetic variability and other factors may influence its therapeutic potential.
- Received December 29, 2008.
- Accepted January 12, 2009.
- Copyright © 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved