Type 1 Diabetes Prevented in Mice

Researchers correct flaw in immune system

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By
HealthDay Reporter

MONDAY, June 7, 2004 (HealthDayNews) -- Researchers have succeeded in preventing type 1 diabetes in mice that were genetically programmed to develop the disease.

Although rodents, in the laboratory as in the field, are a long way from humans, this approach does hold promise for both prevention and treatment.

"It's many, many steps from human adaptation, but it's a big leap in terms of understanding where you can intervene in a specific way," said Dr. Bonita H. Franklin, a clinical associate professor of pediatrics at New York University School of Medicine in New York City.

The study appears in the June 7 issue of the Journal of Experimental Medicine.

Type 1 diabetes is an autoimmune disease in which certain cells from the body's immune system mistakenly attack and destroy the insulin-producing beta cells of the pancreas. Islet cell transplantation is one way by which scientists have been hoping to treat the disease. Although this allows the body to start producing insulin again, it doesn't resolve the underlying immune system dysfunction, requiring individuals to take toxic immunosuppressive drugs.

A key to preventing and treating type 1 diabetes would be to go back a step to correct these underlying immune-system deficiencies. This would be especially helpful in those who have antigens but who have not yet developed the disease. "Finding antigens is the most predictive thing, but then what?" Franklin asked. "What do you do if you know someone is at risk?"

Recently, scientists discovered that a certain type of T-cell in the immune system has a specific regulatory function, meaning they turn off the "killer" cells. When there are enough suppressor cells and they are functioning correctly, they make sure the body doesn't turn on itself.

In people with type 1 diabetes and other autoimmune diseases, however, the balance has been upset. "It appears that regulatory T-cells are either deficient or dysfunctional, quantitatively or qualitatively abnormal, in people with autoimmune diseases," said Dr. Richard Insel, executive vice president of research at the Juvenile Diabetes Research Foundation in New York City, which partially funded the study.

The authors of this study tried to restore the balance by expanding and activating regulatory T-cells in mice, using dendritic cells. Dendritic cells basically screen antigens in the body and tell other immune system cells how to respond.

"They're like a cipher. They look at antigens and determine if this is something foreign or self," Insel explained. "They screen or filter, then they send signals to the immune system, saying, 'Respond aggressively and destructively, or this is something we should tolerate and not respond to.'"

These dendritic cells, it turns out, can be used to "educate" the regulatory T cells.

"A paper from our lab about a year ago showed that in normal mice, dendritic cells would give the signals needed for these [regulatory] cells to proliferate," said study author Kristin Tarbell, a postdoctoral fellow in Rockefeller University's Laboratory of Cellular Physiology and Immunology in New York City. "In this study, I used the dendritic cells to expand the regulatory cells, then used those to block diabetes."

The reprogrammed T-cells were essentially able to turn off the attacking cells, thereby saving the beta cells and warding off diabetes.

"We envision taking blood from a recently diagnosed individual and, from that blood, making dendritic cells, isolate the regulatory T-cells, and then put them together with the islet antigen to get more regulatory cells and put them back in the patient," Tarbell said. "The concept is that we would change the balance of the immune response, and halt autoimmunity."

Although this paper looked specifically at prevention, there is also a potential for this technique to treat the disease.

"This study is important because it takes you back an extra step before the destruction of the pancreas occurs," Franklin said. "If it could be done, it would be very specific. Autoimmunity would be prevented only where you wanted it to be prevented. The rest of the immune system would function fine."

More information

The Juvenile Diabetes Research Foundation has more on the basics of type 1 diabetes.

SOURCES: Richard Insel, M.D., executive vice president, research, Juvenile Diabetes Research Foundation, New York City; Kristin Tarbell, Ph.D., postdoctoral fellow, Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York City; Bonita H. Franklin, M.D., clinical associate professor, pediatrics, New York University School of Medicine, New York City; June 7, 2004, Journal of Experimental Medicine

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