A signaling molecule with an affinity for alcohol appears to have yielded a rapid, inexpensive way to make large numbers of immune cells that work to protect the body from the attack of misguided cells implicated in autoimmune diseases.
The ability to make large numbers of these cells opens the door to improved treatment and a better understanding of autoimmune diseases such as type 1 diabetes and arthritis according to the researchers from the Medical College of Georgia.
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. The Research published in the August issue of Nature Methods shows that, given the option, phospholipase D, which typically mixes with water, prefers alcohol. It kills 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,’ 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% 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 % of all T cells, and isolating them is a long, expensive process.
When researchers gave 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 1 diabetes.
‘Our prediction and our hope is that we can restore balance, the usual 5 to 95 ratio of regulatory cells to non-regulatory T cells is lost in those with autoimmune disease. However, too many regulatory cells also can be a problem’ comments Dr Iwashima, 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 believe.
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 see moderate drinking as beneficial yet. The research was also supported by the National Institutes of Health.
Source: Singh N et al. Enrichment of regulatory CD4+CD25+ T cells by inhibition of phospholipase D signaling. Nature Methods 2006;3:629-36.