Grant: Team Grant: Preparation to Trial: Inflammation for Chronic Conditions

A process called immune tolerance allows the immune system to fend off dangerous foreign substances yet leave the body's own tissues untouched. When immune tolerance fails, autoimmune diseases and/or chronic inflammation occur. There are no medications that promote or replicate immune tolerance. This is particularly problematic for transplant recipients, whose immune systems must be suppressed with medications to prevent rejection. As a result, transplant recipients must live with impaired immune tolerance and chronic inflammation. Our goal is to move beyond symptom management and find long-term solutions. We have been working towards this goal by developing a therapy that takes advantage of a specialized type of white blood cell, called regulatory T cells, or Tregs, which suppress undesired immune responses and promote the formation of an appropriately balanced immune system. Tregs are rare in circulating blood, but we have shown that an organ called the thymus (which is routinely removed and discarded during heart surgery) is an abundant source of easily-isolated, pure Tregs. We have shown that thymus Tregs have beneficial effects in mouse models of transplantation, and now, we aim to conduct a clinical trial to determine if thymus Tregs are a safe and effective way to prevent immune complications after bone marrow transplantation. Data from this proposal will show how to best design the trial and how to best match donor thymus Tregs to the patient. Once we establish safety and effectiveness of thymus Tregs in the context of transplantation, we will be able to extend off-the-shelf Treg therapy to many other inflammatory diseases.