Autoimmune disease breakthrough
Published: August 9, 2006
A signalling molecule with a penchant for alcohol has highlighted a quick and inexpensive way to make large numbers of immune cells stop the misguided cells from attacking the body.
According to Medical College of Georgia (MCG) researchers, the ability to easily make large numbers of these cells opens the door to improved treatment and a better understanding of autoimmune diseases such as type1 diabetes and arthritis.
T cells are a component of the immune system called upon to attack invaders, such as bacteria and viruses, and a smaller subset of T cells are regulators that prevent the cells from attacking body tissues.
Research published in the August issue of Nature Methods shows that, given the option, phospholipase D, which typically mixes with water, prefers alcohol.
It’s an apparently lethal choice for the signalling molecule that, in turn, also kills T cells that need phospholipase D to survive – previously, it was unknown whether regulatory T cells required the molecule.
“What we have found is that if you block this enzyme, almost all T cells die after three days but the regulatory T cells can survive,” said Dr Makio Iwashima, MCG immunologist and the study’s corresponding author.
“After three days, we give them some food to grow and, in one week, you get about 90 per cent pure regulatory cells.”
The approach worked with laboratory-grade alcohol, called butanol, as well as beverage-grade ethanol.
Normally, regulatory T cells constitute about two to five per cent of all T cells, Dr Iwashima said, isolating them is doable but a long, expensive process.
When researchers gave some of the regulatory T cells to a mouse model of inflammatory bowel disease, the symptoms, including dramatic weight loss, went away.
Animals showed no classic signs of inflammation, just a significant increase in regulatory cells.
MCG researchers have obtained funding from the Arthritis Foundation and the Juvenile Diabetes Research Foundation to see if the cell therapy will work as well in animal models for arthritis and type1 diabetes.
“Our prediction and our hope is that we can restore balance,” explained Dr Iwashima.
While in the usual five to 95 per cent ratio of regulatory to non regulatory T cells is lost in those with an autoimmune disease, cancer patients suffer higher levels of regulatory cells.
This finding indicates a potential role for helping transplant patients keep new organs, the researchers say.
Dr Iwashima has an Alcoholic Beverage Medical Research Foundation grant to pursue alcohol’s potential for helping isolate desirous regulatory cells.
However, he cautions that his research findings are not a green light for patients with autoimmune disease to drink because of the negative health effects of regular alcohol consumption.
Dr Iwashima and his team believe the best way to optimise cell percentages is to do what the body does, and they already are searching for a naturally-occurring substance that interferes with phospholipase D.
“Ultimately, that is the most natural way, if we can find the compound in our bodies that can do the job,” Dr Iwashima said.
He cautioned that this natural substance helps destroy non-regulatory T cells when the body gets too many, say after fighting a big infection, and that it may not work well enough in people with autoimmune disease.
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