JDRF Research
Possible Mechanism found for Type 1 Diabetes Trigger
A direct pathway through which a virus or dietary factor could disrupt the body’s normal immune function and trigger type 1 diabetes has been uncovered by researchers at the JDRF/Beverly Berry Center for Immunological Tolerance in Type 1 Diabetes at Harvard Medical School. The study suggests that the immune system goes awry by overreacting to foreign matter entering the pancreatic lymph nodes. In response, T cells within the pancreatic lymph nodes increase ranks and destroy everything, including the body’s own insulin cells.
“This finding is another an important step in identifying the triggers of type 1 diabetes,” said JDRF Executive Vice President for Research Richard Insel, M.D. “Researchers will now increase focus on this intersection of “self” and “non-self” antigens as they develop strategies to block the disease.”
When it is functioning normally, the immune system is able to distinguish between self (the body’s own cells) and non-self (foreign material) to defend the body against toxins or bacteria (antigens) without inflicting damage through “friendly fire.” In people with type 1 diabetes and other autoimmune diseases, the immune system mistakenly responds to the body’s own molecules, or “self antigens,” and launches an attack on the body’s cells. Previous research had shown that lymph nodes draining the pancreas, rather than the pancreas itself, make up ground zero for the autoimmune response. At that site, T cells first become incited into action and go on the attack against insulin-producing beta cells. But scientists do not know what triggers the destruction, or which route whatever prompted the attack may take to get to the lymph nodes.
The Joslin research, conducted in mice, shows that the T cells in the pancreatic lymph nodes encounter antigens deriving from the intestinal tract, which may contain foreign material. This event instructs the T cells to recognize and destroy cells bearing the foreign substance.
In most people, this does not cause problems, since T cells are not sufficiently activated to destroy anything beyond the foreign material. But in people genetically at risk for type 1 diabetes, certain viral or dietary elements may profoundly affect the T cell response, triggering a cascade that destroys the beta cells. Dr. Insel noted that it’s as if the mixture of self and non-self throws the normally precise immune response into disarray and causes it to demolish cells indiscriminately.
The study was published in the December 6 issue of the Proceedings of the National Academy of Sciences by Diane Mathis, Ph.D., Christophe Benoist, M.D., and fellow researchers at the Joslin Diabetes Center at Harvard.
If additional research confirms that the same convergence of self and non-self antigens occurs in human pancreatic lymph nodes, scientists will have a clearer target for intervening in the encounter between the T cells and foreign antigens and possibly blocking the first stage of the disease.