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Immune restoration following hematopoietic stem cell transplantation: an evolving target

Bone Marrow Transplantation volume 35, pages 835–857 (2005)Cite this article

Summary:

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.

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Acknowledgements

We would like to acknowledge the important work of clinicians and basic science researchers whose efforts were not included in this review due to space limitations. In addition, we would like to thank Drs Pavan Reddy and David Porter for their critical review of this paper. Dr Auletta's research is supported by grants from the NIH (AI 57801) and the Center for Stem Cell and Regenerative Medicine at Case Western Reserve University.

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  1. Comprehensive Cancer Center, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, USA

    J J Auletta & H M Lazarus

  2. Department 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

    J J Auletta

  3. Department of Medicine, Division of Hematology/Oncology, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    H M Lazarus

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  1. J J Auletta
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Correspondence to J J Auletta.

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Auletta, J., Lazarus, H. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant 35, 835–857 (2005). https://doi.org/10.1038/sj.bmt.1704966

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