They found significantly fewer iNKT cells in the thymus, spleen, liver and bone marrow and severely impaired maturation of those cells in mice missing the Aire gene. And the mice given alpha-GalCer had significantly reduced autoantibody production.
In 2001, Dr. Terry L. Delovitch and his colleagues at Canada's Robarts Research Institute, including Dr. Mi, reported in Nature Medicine that using alpha-GalCer to boost iNKT cells and re-establish a healthy balance of good and bad immune cells prevented development of type 1 diabetes in an animal model for the disease.
But Drs. Mi and She say new iNKT boosters likely are needed because the action of alpha-GalCer somehow depends on individual genetic architecture as well as other factors. Under certain conditions, the drug can help or worsen an autoimmune disease by producing good or bad cytokines. That's why it also has worked for some cancers and why a modified version of the glycolipid or totally different drugs may work better, Dr. She says. "By understanding more, we are better able to come up with better targets," he says.
"iNKT development is still the big question," says Dr. Mi. "Not only how they develop, but how they develop properly."
The researchers watched the key regulatory cells come out of the bone marrow and go to the thymus where all T cells go for a process of positive and negative selection and maturation. Positive selection eliminates cells that are dysfunctional. Negative selection is eliminating T-cells that recognize the body's own proteins, Dr. She says.
Other researchers recently confirmed that the Aire gene is involved in negative selection by controlling some protein expression in the thymus, Dr. Mi says. The thymus is supposed to express most body proteins so any T cells that would react to them can be eliminated through negative se
Source:Medical College of Georgia