Same. Part II.
Potential new therapy for type 1 diabetes described
Last Updated: 2001-08-30 10:14:22 EDT (R@uters Health)
LONDON (R@uters Health) - By activating natural killer T cells (NKT cells), alpha-galactosylceramide (alpha-GalCer) can prevent the onset and recurrence of autoimmune type 1 diabetes, according to the findings of two studies published in the September issue of Nature Medicine.
The number and function of NKT cells, which appear to control beta-cell reactive T cells, are reduced in people with type 1 diabetes. The current studies investigated one possible method of activating NKT cells and thereby preventing pancreatic autoimmune destruction.
In one study, Dr. Terry L. Delovitch, from the University of Western Ontario in London, Canada, and colleagues treated female non-obese diabetic (NOD) mice with alpha-GalCer. They found that even when given after the onset of insulitis, alpha-GalCer prevented the development of type 1 diabetes in the mice.
Furthermore, alpha-GalCer prolonged the survival of pancreatic islet cells that were transplanted into newly diabetic NOD mice. Interleukin-7 coadministration seemed to potentiate the effects of alpha-GalCer.
The effects of alpha-GalCer were linked to suppression of T- and B-cell autoimmunity to islet beta cells and to a polarized Th2-like response in the spleen and pancreas of test animals, the authors determined.
"Our data point to a new approach for prevention of onset and recurrence of type 1 diabetes by targeting NKT cells," the researchers state. "Although alpha-GalCer is hepatotoxic in mice, it lacks severe toxicity in humans."
Dr. Luc Van Kaer, from Vanderbilt University in Nashville, Tennessee, and colleagues performed a similar study involving NOD mice and found that alpha-GalCer prevented diabetes only in mice with an intact CD1d antigen presentation pathway.
The investigators also found that alpha-GalCer's anti-diabetic activity correlated with its ability to selectively suppress interferon-gamma production by NKT cells, to increase serum immunoglobulin E levels, and to promote generation of islet autoantigen-specific Th2 cells.
"Collectively, our findings identify NKT cells as novel targets for immunotherapy," Dr. Kaer's team notes. "Because recognition of alpha-GalCer by NKT cells is phylogenetically conserved, our studies are directly relevant to modulation of human autoimmune diseases."
Nat Med 2001;7:1052-1062. |
