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-α and TNF-α, 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.
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7 February 2005
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February 07 2005
Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment
Isabelle J. Fugier-Vivier,
Isabelle J. Fugier-Vivier
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
2Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202
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Francine Rezzoug,
Francine Rezzoug
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Yiming Huang,
Yiming Huang
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Amanda J. Graul-Layman,
Amanda J. Graul-Layman
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Carrie L. Schanie,
Carrie L. Schanie
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Hong Xu,
Hong Xu
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Paula M. Chilton,
Paula M. Chilton
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Suzanne T. Ildstad
Suzanne T. Ildstad
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
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Isabelle J. Fugier-Vivier
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
2Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202
Francine Rezzoug
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
Yiming Huang
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
Amanda J. Graul-Layman
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
Carrie L. Schanie
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
Hong Xu
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
Paula M. Chilton
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
Suzanne T. Ildstad
1Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202
CORRESPONDENCE Suzanne T. Ildstad: [email protected]
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.
Received:
July 12 2004
Accepted:
October 15 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 201 (3): 373–383.
Article history
Received:
July 12 2004
Accepted:
October 15 2004
Citation
Isabelle J. Fugier-Vivier, Francine Rezzoug, Yiming Huang, Amanda J. Graul-Layman, Carrie L. Schanie, Hong Xu, Paula M. Chilton, Suzanne T. Ildstad; Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment . J Exp Med 7 February 2005; 201 (3): 373–383. doi: https://doi.org/10.1084/jem.20041399
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