Our research seeks to determine how auto-aggressive or "self reactive" T cells cause autoimmune diseases such as Type 1 (juvenile) Diabetes and Multiple Sclerosis (MS).
T cells normally respond to foreign antigens such as bacteria, virus, fungus or parasitic infections even tumors. T cells recognize antigens through their T cell receptor (TCR) molecules which are specifically expressed so that one T cell for example recognizes an antigen from influenza and another T cell recognizes antigen from Streptococcus B. However, during an autoimmune disease, T cells incorrectly identify self-tissue as being foreign and therefore respond. This response results in inflammation that is persistent and ultimately destroys the normal tissue. In the case of type 1 diabetes (T1D), T cells recognize the islet cells of the pancreas (the cells that produce insulin) and destroy them, thus preventing insulin production which leads to high blood sugar.
Our laboratory is focused on three research areas: 1) Generation of auto-aggressive T cells; 2) A means of controlling auto-aggressive T cells and 3) The role of T cells as culprits in a multitude of diseases such as MS, Chronic Obstructive Pulmonary Disease, Lupus, T1D and other diseases.
At the Webb-Waring Center, we identified the T cells that are responsible for causing T1D. We found a biomarker, CD40, which identifies pathogenic T cells and showed that these T cells specifically attack the islet cells of the pancreas and lead to destruction of insulin producing cells.
Additionally, we are exploring the way that the CD40-positive T cells (Th40 cells) develop in diabetes and other autoimmune diseases. We have determined that Th40 cells can alter the expression of their T cell receptor, in other words the way they recognize antigens. We are determining how to change Th40 cells so that they no longer cause disease. These findings will lead to better treatments for auto-immune disease; however, we will need to control the T cells that damage the normal system, without destroying the overall immune system.
We have discovered that Th40 cells are radically expanded in human T1D and MS subjects. This finding suggests that these T cells are involved in the disease process. We have confirmed that Th40 cells from T1D and MS subjects respond to known self antigens suggesting that these T cells cause disease.
Statistics from the Centers for Disease Control and Prevention show that more than 32 million Americans are afflicted by some form of Arthritis which affects 125 of every 1000 people under the age of 45, and almost half of the people aged 45 to 64. Diabetes was responsible for 63,000 deaths in 1997 making it the seventh leading cause of death in people 18 to 64 years.