The Barbara Davis Center remains in the forefront of investigation aimed at identifying the immune cells (lymphocytes) responsible for the pathogenesis of Type 1 diabetes. One of the most striking results has come from Dr. Dale Wegmann's laboratory group which has examined the nature of the lymphocytes (specifically the thymus-derived T cells) that attack pancreatic islets. Using a mouse model of Type 1 diabetes, which is very similar to the human disease, the non-obese diabetic (NOD) mouse, Dr. Wegmann's group has found that a large proportion of T cells that attack the pancreatic islets recognize a portion of the insulin molecule itself as a target structure. Further, these insulin-reactive T cells can initiate disease when injected into non-diseased animals. These studies represent the first clear demonstration of a defined islet-specific target structure involved in the pathogenesis of Type 1 diabetes.
Perhaps equally important are more recent studies showing that appropriate innoculation of NOD mice with these insulin fragments at a young age will actually prevent or delay the subsequent onset of diabetes. Our hope is that these exciting new studies can be translated into effective therapies to prevent diabetes in man.
Another related arm of research at the Center continues to focus on islet cell transplantation as a treatment for existing Type 1 diabetes. Type 1 diabetes forms a formidable dilemma for the field of transplantation. In organ transplantation, such as with kidney or heart grafting, the transplant recipient must receive non-specific chemical immunosuppressive drugs to prevent immune rejection of the transplant. Currently, these immunosuppressive agents have a number of potentially serious side effect, but are justified because the transplant is necessary to sustain life. However, unlike other conditions of organ failure, Type 1 diabetes is not immediately life-threatening,and so the use of conventional immunosuppressive agents is not justified except in extreme cases where the Type 1 diabetic recipient is already receiving a kidney transplant due to renal failure. As such, the goal of research at the Center continues its focus on islet cell transplantation using minimal receipient immunosuppression. Like many investigators worldwide, Dr. Marilyne Coulombe has performed a series of studies that demonstrate that it is possible to transplant foreign islet tissue into animals without immune suppression by pre-treating the donor islet tissue in order to reduce the ability of the tissue to elicit an immune reaction in the recipient.
Another major problem in islet transplantation is that the autoimmune damage that produces the original damage in Type 1 diabetes may also recur in an islet transplant. While this phenomenon of disease recurrence is islet cell transplants has been well-documented in animal models by several groups, including work performed at the Center, disease recurrence in clinical islet transplants has been less clear. Very preliminary studies performed by investigators at the Center have indicated that islets transplanted into human Type 1 diabetic recipients are also destroyed by an immune response that appears very similar to that found in the NOD mouse. Thus, the underlying autoimmunity in Type 1 diabetes may be an important obstacle in human islet transplantation.
As investigators get a better understanding of the immune cells that trigger islet destruction in this disease, our two-fold goal will be to apply this understanding toward preventing the development of diabetes in patients who are at risk for the disease, and controlling the immune system recognition of islet transplants.
Children's Diabetes Foundation at Denver
777 Grant Street, Suite 302
Denver, Colorado 80203
Barbara Davis Center for Childhood Diabetes
1775 Aurora Ct.
Aurora, CO 80045
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