Research Area
Diabetes

Grant Type
Fellowship

Year
2007

Abstract

Under normal circumstances the immune system is able to distinguish normal tissues from abnormal tissues, and can specifically target the abnormal tissue or an invading organism. However, when the immune system becomes disregulated, it can destroy normal tissue, leading to autoimmunity. In Type I Diabetes, T cells specifically target the insulin-producing cells of the pancreas. In order to understand the environment that exists for treatments such as islet transplantation into diabetic individuals, it is important to understand how these T cells become activated and how they affect the activation of other T cells.

Our goal is to determine whether diabetes onset and persistence is maintained by positive feedback loops between antigen-presenting cells (APCs) and T cells. We aim to establish how subsets of autoantigen-specific T cells induce increased autoantigen presentation through interactions with existing APCs as well as with each other. We hypothesize that critical frequencies of diabetogenic T cells induce a sharp rise in autoantigen-presenting APCs in the draining lymph node. We will further examine whether specific subsets of T cells augment this autoimmune feedback loop more than others and how these subsets alter the landscape for new T cells to be activated and reactivated in the lymph node. Finally, we will assess the influence of direct T-T interactions on T cell activation during the response to autoantigens to test the hypothesis that coordinated activities of multiple cell types induce and maintain the autoimmune state.