Joslin Diabetes Center researchers Diane Mathis’s and Christophe Benoist’s finding that the lymph node draining the pancreas was intrinsic to the autoimmune response in mice made David Hafler, HMS professor of neurology at Brigham and Women’s Hospital, wonder if something similar was happening in people. In the May 12, 2005 Nature, he and his colleagues report that about one quarter of the CD4 T cells cloned from the pancreatic lymph nodes of two diabetic women were reactive to insulin excreted by islets.
T cells from two healthy people and one person with type 2 diabetes showed no expansion of insulin-reactive T cells. In another experiment, T cells from the spleen of one of the two women showed no reaction to insulin.
In another paper, Denver researchers prevented diabetes in mice by replacing their insulin genes with one missing the autoreactive epitope. Female mice with the altered insulin did not develop insulin autoantibodies, the T cell invasion of islet cells known as insulitis, or autoimmune diabetes.
“It looks like this epitope is crucial for the initiation of disease,” said senior author George Eisenbarth, executive director of the Barbara Davis Center for Childhood Diabetes at the University of Colorado Health Sciences Center.