Treg Specificity and Development Project

The thymus is and important source of Tregs. Removal of the mouse thymus 3 days after birth results in autoimmunity due to the lack of Tregs. Approximately 5-10% of CD4+ T cells that develop in the thymus are Tregs. The cellular and molecular mechanisms responsible for Treg development are currently unknown. It has been proposed that these Tregs express autoreactive T cell receptors, and that the signals received through this autoreactive receptor may be responsible for their development. This project focuses on examining the specificity of the T cell receptors expressed by Tregs, and determining the effects of expressing these T cell receptors on CD4+ T cell development. The goal is to learn about the specificity the T cell receptors expressed by Tregs in order to have a better understanding of how they prevent autoimmune disease, and influence immune responses to infection.

Autoimmunity Project

There are more than 80 different autoimmune diseases that affect approximately 50 million people in the United States alone. Autoimmunity develops when the immune system, which normally protects the body from pathogens, instead attacks cells or tissues in the body. Juvenile diabetes, multiple sclerosis, rheumatoid arthritis, and lupus are a few examples of autoimmune diseases. Currently there are no cures for autoimmunity, and immunosuppressive drugs, which suppress the entire immune system, are use to treat many diseases. These drugs can sometimes slow the disease process, but also cause individuals to be more susceptible to infections and have harmful side effects. The discovery of the immunosuppressive activity of regulatory T cells has led to a lot of excitement because of the potential to develop new therapies to target immunosuppression to specific tissues, and avoid the negative effects of immunosuppressive drugs. This project utilizes a well defined autoimmune disease model to examine the how tissue specific Tregs can influence various cellular and molecular processes during the course of an autoimmune disease. This research will provide valuable insight as to whether Tregs can be used to suppress the immune system in a specific manner, which will be useful in the development of new therapies for autoimmune diseases, and perhaps in other cases where immunosuppressive drugs are used, such as preventing organ rejection after transplantation.

Autoimmune gastritis is a model of organ specific autoimmune diseases. Like many other autoimmune diseases, autoreactive CD4+ T cells are important in the development of disease. Disease is initiated by injecting CD4+ T cells specific for H+/K+ ATPase, a protein expressed by parietal cells in the stomach into mice. These mice are then injected with CD4+FoxP3+ Tregs specific for H+/K+ ATPase at various stages of the disease process to determine whether they can inhibit or reverse the course of Autoimmune Gastritis. A combination of cellular and molecular assays are performed to understand how these Tregs are affecting the various stages of disease.