Dendritic cells in allogeneic hematopoietic stem cell transplantation

Abstract

In allogeneic hematopoietic stem cell transplantation (SCT), dendritic cells (DCs) as the most potent antigen-presenting cells play a central role in the development of acute and chronic graft-vs-host disease (GVHD), in graft-vs-leukemia or -malignancy reactions and in fighting infectious complications. Functional maturity and distribution of DC sub-types (DC1 and DC2) differ between the different stem cell sources used (bone marrow, granulocyte colony-stimulating factor-mobilised peripheral blood and cord blood) resulting in various rates of graft-vs-host disease and graft-vs-leukemia activity. Although DC recovery following stem cell transplantation is prompt, graft-vs-host disease and the use of immunosuppressive drugs result in qualitative and quantitative disturbances in DC homeostasis and have been observed for up to 1 year after transplantation. Complete donor DC chimerism seems to be a pre-requisite for the development of chronic GVHD and for graft-vs-leukemia activity, at least following reduced-intensity transplants, although in the early phase of acute graft-vs-host disease the presence of host antigen-presenting cells is essential. Preliminary data show promising results with DC-based immunotherapy for treatment of viral and fungal infections and of leukemic relapse following allogeneic stem cell transplantation. More information on the mechanisms and interactions between dendritic cells and regulatory T cells is needed for DC vaccination concepts for modulation of graft-vs-host disease.

Keywords:

• Dendritic cells
• allogeneic stem cell transplantation
• graft-versus-host disease