CD4+CD25+regulatory T cells in human hematopoietic cell transplantation

Naturally occurring CD4(+)CD25(+) regulatory T cells (T-reg)are differentiated T lymphocytes actively involved in the control of peripheral immunity. Over the past few years, a number of animal studies have demonstrated the critical role of these cells in the outcome of allogeneic hematopoietic stem cell transplantation (HCT). In these models T-reg can exert a potent suppressive effect on immune effector cells reactive to host antigens and prevent graft versus host disease (GVHD) while preserving the graft-versus-leukemia effect (GVL). The present review summarizes current knowledge on the role of T-reg populations in humans following allogeneic HCT. Recent investigations focusing on T-reg in transplant patients have generated conflicting results mostly due to the use of different parameters to assess T-reg. Nonetheless, these studies suggested that an imbalance between T-reg and effector cells during immune reconstitution can substantially impair regulatory mechanisms and contributes to the development of GVHD. Building on these studies, a number of therapeutic strategies are being developed to positively modulate T-reg pools in vivo and prevent or even correct GVHD. Conversely, clinical interventions can also be envisaged to decrease T-reg activity in vivo and enhance the GVL effect. These potential strategies are discussed herein. Coining years will undoubtedly yield additional knowledge on how to use T-reg subsets in vivo and successfully control and modulate immune responses in patients post-HCT. (c) 2005 Elsevier Ltd. All rights reserved.