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The role of pDC, recipient Treg, and donor Treg in HSC engraftment

P. Cárdenas,Yiming Huang,S. Ildstad

Published 2011 in Chimerism

ABSTRACT

Hematopoietic stem cell (HSC) transplantation (HSCT) has been utilized for treatment of many hematologic malignancies, genetic and metabolic disorders, and hemoglobinopathies such as sickle cell disease and thalassemia. It also induces donor-specific tolerance to organ and tissue transplants. The widespread success of HSCT is hampered by the toxicities of immunosuppression and development of graft-versus-host disease (GVHD). The mechanism of induction of transplantation tolerance (reciprocal donor/host) is still an elusive challenge in allogeneic HSCT. An understanding of the mechanisms for induction of tolerance and the critical cells involved in this process has resulted in novel cell-based therapies poised to be translated to clinical application. The focus of this review is those cells of interest. Bone marrow-derived plasmacytoid dendritic cells induce naïve T cells to differentiate to become antigen-specific regulatory T cells (Treg), creating a milieu for the induction of transplantation tolerance. Recently, CD8+/TCR- facilitating cells (FC), a novel cell population in mouse bone marrow, have been shown to potently enhance engraftment of allogeneic HSC without causing GVHD. The predominant subpopulation of FC resembles plasmacytoid precursor dendritic cells. FC induce antigen-specific Treg in vivo. Notably, FC address one major concern that has prevented the implementation of Treg cell therapy in the clinic: to expand Treg and have them remain tolerogenic in vivo. FC are novel in that they induce an antigen-specific regulatory milieu in vivo. The discovery of FC has opened new alternatives to expanded criteria in bone marrow transplantation that were previously restricted to human leukocyte antigen-matched recipients. The focus of this review is to cover what is currently known about the mechanism of FC action in inducing tolerance and preventing GVHD and host-versus-graft reactivity.

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