Phenotypic and functional characterization of T regulatory cells

FOXP3⁺ T regulatory cells (Tregs) normally function to restrain immune responses, but when their activities go awry diseases such as autoimmunity and cancer can result. Animal models have proven that enhancing or inhibiting the function of Tregs is an effective way to prevent, and in some cases cure, many immune-mediated diseases. Approaches to specifically modulate the activity of Tregs are already being translated to humans, yet we know remarkably little about how Tregs achieve their potent immunosuppressive effects. The aim of this research was to further understand the factors that regulate the molecular phenotype and functionality of Tregs in order to better use them for therapeutic purposes. To achieve this goal, the interaction between Tregs and adenoviral-transduced human monocyte-derived dendritic cells in the context of cancer immunotherapy was explored. I found that these genetically-engineered DCs designed to boost the immune response were still susceptible to Treg suppressive influence. Next, I investigated the biological relevance of chemokine secretion by Tregs and determined that chemokine-mediated active recruitment of their targets of inhibition may be a novel mechanism of action. Finally, I established a human Treg-specific gene signature using Affymetrix microarray technology in order to define better ways to isolate and track these cells. Taken together, these studies have contributed significantly to understanding how Tregs exert their homeostatic control of immunity and revealed potential tactics to manipulate their activity in clinical aspects.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat