'Lazy' T-cells can trigger diabetes

Source: McGill University

A Canadian research team has confirmed that the T-cells that regulate the body's autoimmune reactions lose their effectiveness over time, leading to the onset of type 1 diabetes.

The team, led by Dr Ciriaco Piccirillo of McGill University's Department of Microbiology and Immunology, published its findings in the January 2008 edition of the journal Diabetes.

The study was conducted on non-obese diabetic (NOD) mice, which were genetically engineered to model human diabetes.

In diabetes mellitus, or type 1 diabetes, insulin-producing beta islet cells in the pancreas are attacked and destroyed by the body's own immune system.

"The genetic and cellular mechanisms by which the immune system goes out of control and destroys the islets has been an enigma and an area of great interest over the last few decades," Piccirillo said.

"For the last several years, it's been postulated that non-functional regulatory T-cells are the critical mechanism, and this study proves it." Regulatory CD4+ T-cells, whose development and function is dictated by the Foxp3 gene in mice and humans, "have the primary function of pouring a cold shower on inflammatory responses," he said.

"They suppress and regulate the function of various immune responses to microbes, tumours, allergens and transplants."

While the diabetes-susceptible NOD mice actually generate normal numbers of Foxp3 T-cells over their lifetimes, Piccirillo and his colleagues discovered that the T-cells' functional potency declined with age, leaving potential autoimmune responses in the pancreas unchecked.

It is likely, the researchers say, that certain genetic predispositions, coupled with the possible contribution of external environmental factors or infections, could potentially alter regulatory T-cell function in susceptible individuals and trigger a full-scale diabetic autoimmune reaction in the pancreas.

"Once they start, these immune responses are like a fire that goes unchecked by firemen, or a car going downhill without brakes." Moreover, he said, this discovery not only elucidates the mechanism by which type 1 diabetes is triggered, but it also points the way to the development of new immune system-based therapies for a whole range of diseases.

"We believe that these regulatory cells may represent a kind of master switch, and by understanding how they are made, how they function and how they survive, we may be able to stop disease from occurring."