TID is an autoimmune disease that occurs when the body's immune system mistakenly launches an attack on the insulin-producing cells of the pancreas. Scientists know that very early in disease development immune cells called CD8+ T lymphocytes, which normally protect the body from cancer cells and cells infected with viruses or bacteria, mistakenly invade and damage the pancreas.
The non-obese diabetic (NOD) mouse is an excellent model of human TID. Invasion of the pancreas by CD8+ T cells is observed in 3-week-old NOD mice but diabetes does not develop until 10–20 weeks later. To examine what occurs between T cell infiltration and full-blown diabetes in NOD mice, Dr. Lewis L. Lanier from the Department of Microbiology and Immunology and the Cancer Research Institute at the University of California, San Francisco, and colleagues, together with Dr. Jeffrey Bluestone from the UCSF Diabetes Center, examined a molecule called NKG2D that is found on the surface of CD8+ T cells and binds to certain proteins found only on abnormal cells. When NKG2D recognizes and binds to proteins on abnormal cells, the T cells become activated and destroy the abnormal cells.
"We found that T cells infiltrating the pancreas of NOD mice expressed NKG2D and that the islet cells in the pancreas of pre-diabetic NOD mice, but not normal healthy mice, expressed the NKG2D-binding proteins," explains Dr. Lanier. Dr. Koetsu Ogasawara, a postdoctoral fellow in the Lanier lab, went on to show that treatment of NOD mice with an antibody that blocks the interaction between NKG2D on T cells and NKG2D-binding proteins on pancreas completely prevented diabetes development at a late pre-diabetic stage.
According to Dr. Lanier, "We observed no side effects of anti-NKG2D treatment, suggesting that it may be an efficient therapy for prevention or control of diabetes. We are encouraged by our finding that anti-NKG2D is effective at preventing diabetes even when administered late during disease progression. This is in striking contrast with most treatments reported in the NOD mouse, which are only effective when administered at a much younger age." These results support other recent findings suggesting that, while NKG2D provides protection against cancer and infected cells, it may have a detrimental role in some autoimmune disorders.
Kouetsu Ogasawara, Jessica A. Hamerman, Lauren R. Ehrlich, Helene Bour-Jordan, Pere Santamaria, Jeffrey A. Bluestone, and Lewis L. Lanier: "NKG2D Blockade Prevents Autoimmune Diabetes in NOD Mice"
Published in Immunity, Volume 20, Number 6, June 2004.
Journal
Immunity