Director of Diabetes and Transplant Immunobiology: Pratima Bansal-Pakala, Ph.D.
Insulin dependent diabetes is caused due to the destruction of islet beta cells in the pancreas by self-reactive T cells. In healthy individuals, immune cells are responsible for clearing viral and bacterial infections and self tissues are protected by tolerizing T cells reactive to self proteins. However, in autoimmune diseases, such as diabetes, tolerance of self protein-reactive T cells is disrupted allowing these activated T cells to attack self tissues and lead to destruction and autoimmune disease.
The precise mechanisms involved in breaking of self-tolerance are not clearly elucidated. We have recently shown that OX40, a newly described stimulatory molecule present on the surface of the T cells, can effectively break tolerance of the T cells. We propose to study the role of OX40 in breaking self-tolerance and devise strategies to block the break in tolerance. To examine the role of OX40-mediated signals in tolerance disruption of islet-specific T cells, we will utilize well characterized spontaneous diabetes model, NOD. The first part of the proposal will determine the involvement of OX40 and its ligand during development of diabetes. Second part of the project will study the effect of blocking OX40 signals in prevention of the spontaneous disease progression. Finally, we will evaluate the mechanism of protection afforded by blocking OX40 signals.
The data obtained from these studies will enhance our understanding of the precise mechanisms involved in the development of autoimmune diabetes. The effectiveness of blocking OX40 signals in restoring self-tolerance and preventing disease progression will be important in identifying OX40 as potential therapeutic target.
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