Molecule with a Liking for Alcohol Boosts Regulatory T Cells

[Guest guest]

Finding paves way for better treatment of autoimmune disease

Toni Baker

Aug. 4, 2006

A signaling molecule with an affinity for alcohol has yielded a

rapid, inexpensive way to make large numbers of immune cells that

work like beat cops to keep misguided cells from attacking the body.

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, Medical College of

Georgia researchers say.

T cells are components of the immune system designed to attack

invaders such as bacteria and viruses; regulatory T cells are a small

subset that prevents the cells from also attacking body tissue.

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 signaling

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, "

says 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 percent pure regulatory

cells. "

The approach worked with laboratory-grade alcohol, called butanol, as

well as beverage-grade ethanol.

Normally, regulatory T cells constitute about 2-5 percent of all T

cells, Dr. Iwashima says. 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 type

1diabetes.

" Our prediction and our hope is that we can restore balance, " says

Dr. Iwashima. The usual 5- to 95-percent ratio of regulatory cells to

non-regulatory T cells is lost in those with autoimmune disease, he

says. However, too many regulatory cells also can be a problem, he

says, noting that cancer patients have higher levels of regulatory

cells.

Regulatory T cell therapy also resolved symptoms in a model of graft

versus host disease, a problem for some bone marrow transplant

patients when immune cells from the donor start attacking. 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 colleagues believe the best way to optimize cell

percentages is to do what the body does. In fact, they already are

searching for an endogenous 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 says. He

theorizes 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.

The research was supported by the National Institutes of Health.