1. ¹Comprehensive Cancer Center, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, USA
2. ²Department of Pediatrics, Divisions of Pediatric Hematology/Oncology and Infectious Diseases, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, USA
3. ³Department of Medicine, Division of Hematology/Oncology, Case Western Reserve University School of Medicine, Cleveland, OH, USA

Correspondence: Dr JJ Auletta, Department of Pediatrics, Divisions of Pediatric Hematology/Oncology and Infectious Diseases, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, MS 6054, 11100 Euclid Avenue, Cleveland, OH 44106, USA. E-mail: jeffery.auletta@case.edu

Received 22 February 2005; Accepted 22 February 2005; Published online 21 March 2005.

Abstract

Hematopoietic stem cell transplantation (HSCT) is the definitive cure for many malignant and nonmalignant diseases. However, delays in immune reconstitution (IR) following HSCT significantly limit the success of transplantation and increase the risk for infection and disease relapse in the transplant recipient. Therefore, ways to measure and to manipulate immune recovery following HSCT are emerging and their success depends directly upon an enhanced understanding for the underlying mechanisms responsible for reconstituted immunity and hematopoiesis. Recent discoveries in the activation, function, and regulation of dendritic cell (DC), natural killer (NK) cell, and T-lymphocyte subtypes have been critical in developing immunotherapies used to prevent graft-versus-host disease and to enhance graft-versus-leukemia. For example, regulatory T cells that induce tolerance and NK receptor–tumor ligand disparities that result in tumor lysis are being used to minimize GVHD and tumor burden, respectively. Furthermore, expansion and modulation of immune effector cells are being used to augment hematopoietic and immune recovery and to decrease transplant-related toxicity in the transplant recipient. Specifically, DC expansion and incorporation into antitumor and anti-microbial vaccines is fast approaching application into clinical trials. This paper will review our current understanding for IR following HSCT and the novel ways in which to restore immune function and decrease transplant-related toxicity in the transplant recipient.