Diabetes and Cellular Sloth

Ciriaco A. Piccirillo of McGill’s Department of Microbiology and Immunology and Centre for the Study of Host Resistance (MUHC)
Ciriaco A. Piccirillo of McGill’s Department of Microbiology and Immunology and Centre for the Study of Host Resistance (MUHC)

A new study, led by Ciriaco A. Piccirillo of McGill’s Department of Microbiology and Immunology and Centre for the Study of Host Resistance (McGill University Health Centre), proves a longstanding hunch that waning immunosuppressive T-cells, called regulatory T-cells, play a key role in the onset of type 1 diabetes. The team’s findings were published in the January 2008 issue of the journal Diabetes.

Working with non-obese diabetic mice, Piccirillo’s team discovered that the CD4+ T-cells, expressing the Foxp3 gene, which regulate autoimmune reactions, may lose their effectiveness and become “lazy” over time. These regulatory T-cells normally suppress various immune responses, but when they lose their potency with age they’re no longer able to curb certain autoimmune responses—thus allowing the body to destroy insulin-producing beta islet cells in the pancreas.

The genetic and cellular mechanisms behind this immune system malfunction have long been a mystery. “For the last several years, it’s been postulated that non-functional regulatory T-cells are the critical mechanism,” says Piccirillo, who is the Canada Research Chair in Regulatory Lymphocytes of the Immune System, and a leader in this research area. “Now this study proves it.”

Piccirillo says it’s likely that certain genetic predispositions, possibly coupled with external environmental factors or infections, could alter regulatory T-cell function in susceptible individuals and trigger a full-scale diabetic autoimmune reaction in the pancreas. “Once they start,” he says, “these immune responses are like a car without brakes.”

Type 1 diabetes patients must regularly inject insulin to avoid potentially fatal diabetic shock; secondary health problems include blindness, heart attack and stroke. Piccirillo is optimistic that his team’s discovery may lead to the development of new immune system-based therapies for the disease, and a host of other autoimmune and chronic inflammatory disorders. “We believe that these regulatory T-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.”


This research is funded by CIHR and the Canadian Diabetes Association.