The Journal of Experimental Medicine
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Published 7 February 2005. doi:10.1084/jem.20041399
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 3, 373-383
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ARTICLE

 Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment

Isabelle J. Fugier-Vivier1,2, Francine Rezzoug1, Yiming Huang1, Amanda J. Graul-Layman1, Carrie L. Schanie1, Hong Xu1, Paula M. Chilton1, and Suzanne T. Ildstad1

1 Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
2 Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202

CORRESPONDENCE Suzanne T. Ildstad: suzanne.ildstad{at}louisville.edu

Bone marrow transplantation offers great promise for treating a number of disease states. However, the widespread application of this approach is dependent upon the development of less toxic methods to establish chimerism and avoid graft-versus-host disease (GVHD). CD8+/TCR– facilitating cells (FCs) have been shown to enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic recipients without causing GVHD. In the present studies, we have identified the main subpopulation of FCs as plasmacytoid precursor dendritic cells (p-preDCs). FCs and p-preDCs share many phenotypic, morphological, and functional features: both produce IFN-{alpha} and TNF-{alpha}, both are activated by toll-like receptor (TLR)-9 ligand (CpG ODN) stimulation, and both expand and mature after Flt3 ligand (FL) treatment. FL-mobilized FCs, most of which express a preDC phenotype, significantly enhance engraftment of HSCs and induce donor-specific tolerance to skin allografts. However, p-preDCs alone or p-preDCs from the FC population facilitate HSC engraftment less efficiently than total FCs. Moreover, FCs depleted of preDCs completely fail to facilitate HSC engraftment. These results are the first to define a direct functional role for p-preDCs in HSC engraftment, and also suggest that p-preDCs need to be in a certain state of maturation/activation to be fully functional.

Abbreviations used: CM, chimera media; CSM, cell sort media; FC, facilitating cell; FL, Flt3 ligand; GVHD, graft-versus-host disease; HSC, hematopoietic stem cell; MST, median survival time; p-preDC, plasmacytoid precursor DC; TBI, total body irradiation; TCD, T cell depletion; TLR, toll-like receptor.

I.J. Fugier-Vivier and F. Rezzoug contributed equally to this work.


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