The role of regulatory T cells in graft-versus-host disease management

Introduction: Despite improvements in human leukocyte antigen (HLA) matching algorithms and supportive care, graft-versus-host disease (GVHD) remains the leading cause of non-relapse morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Acute GVHD, typically occurring in the first 100 days post-HSCT, is mediated by mature effector T cells from the donor (graft) that become activated after encountering alloantigens in the recipient (host). Chronic GVHD, characterized by aberrant immune responses to both autoantigens and alloantigens, occurs later and arises from a failure to develop tolerance after HSCT. CD4+ CD25+ CD127- FOXP3+ regulatory T cells (Tregs) function to suppress auto- and alloreactive immune responses and are key mediators of immune tolerance. Areas covered: In this review, authors discuss the biologic and therapeutic roles of Tregs in acute and chronic GVHD, including in vivo and ex vivo strategies for Treg expansion and adoptive Treg cellular therapy. Expert opinion: Although they comprise only a small subset of circulating CD4 + T cells, Tregs play an important role in establishing and maintaining immune tolerance following allogeneic HSCT. The development of GVHD has been associated with reduced Treg frequency or numbers. Consequently, the immunosuppressive properties of Tregs are being harnessed in clinical trials for GVHD prevention and treatment.