Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment.
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.
Fugier-Vivier
Isabelle J
IJ
Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202, USA.
Rezzoug
Francine
F
Huang
Yiming
Y
Graul-Layman
Amanda J
AJ
Schanie
Carrie L
CL
Xu
Hong
H
Chilton
Paula M
PM
Ildstad
Suzanne T
ST
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology; D004247:DNA / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006085:Graft Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010950:Plasma Cells / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology*; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D039521:CD11c Antigen; D016207:Cytokines; D004247:DNA