Sunday, 16 February 2014
Columbus CD (Hyatt Regency Chicago)
A subset of CD4+ T cells derived from the thymus co-express the interleukin-2 receptor (CD25), termed regulatory T cells (Tregs) and upon migration to the periphery are potently immune suppressive and critical for maintaining immune homeostasis. Allogeneic hematopoietic stem cell transplantation has proven to be effective in treating malignant and non-malignant disorders but has as a major complication, graft-versus-host disease (GVHD), a multi-organ system immune complication. In rodents, we and others showed that infusing large numbers of Tregs along with the donor cells prevented GVHD. In humans, Tregs have similar properties but are present in lower frequency. Using cell isolation techniques and in vitro approaches to expand Tregs using microbeads coupled to immunostimulatory antibodies, we performed a first-in-human trial of umbilical cord blood derived Tregs given to patients receiving unrelated donor cord blood transplants for hematological malignancies. We observed no toxicity and a significant reduction but not elimination of GVHD. Since Treg number remained limiting, we developed a cell-based expansion approach to obtain many more Tregs. We are now in the midst of a clinical trial infusing sufficient numbers of Tregs to better test the principle that this suppressor population can markedly reduce GVHD that may eventually lead to the abiilty to forgo immune suppressive drugs entirely. The concept of Treg infusion for restoring immune regulation is now being applied to autoimmune settings such as type I diabetes.