Regulatory T Cell Control of Autoimmune Diabetes and Their Potential Therapeutic Application

Extensive research in animal models and human patients in the past ten years since the mid-1990s has established that regulatory T cells (Tregs) are essential in maintaining normal immune homeostasis. Apart from this fundamental role, both natural and adaptive Tregs function to control various autoimmune disorders including Type 1 diabetes (T1D). These autoantigen-specific Tregs suppress the activation of a wide variety of cells including pathogenic T cells, B cells, and cells of the innate immune system such as dendritic cells, macrophages and granulocytes. The mechanisms of Treg control of autoreactive T cells in T1D are likely two-fold. First, in steady state, Tregs prevent activation of autoreactive T cells in the lymph nodes by limiting their access to dendritic cells and thus their expansion and acquisition of effector functions. These activities are largely mediated by thymus-derived natural Tregs. Second, when immune homeostasis is perturbed and inflammation erupts in the tissues, both natural Tregs and cytokine-induced adaptive Tregs traffic to the site of inflammation and curtail the functions of fully differentiated pathogenic effector T cells in the target tissue. Thus, the ability of Tregs to actively control unwanted immunity even after the onset of pathological manifestation makes them an attractive candidate of immunotherapy for autoimmune diseases such as T1D.