title: CD123bright plasmacytoid predendritic cells: progenitors undergoing cell fate conversion?
abstract: CD123(bright) plasmacytoid cells (PC) and CD1c(+) peripheral blood myeloid dendritic cells (DC) are two human DC precursors that can be expanded in vivo by Fms-like tyrosine kinase 3 ligand (FL). It has been proposed that PC and myeloid CD1c(+) DC may represent two distinct lineages of DC. However, the phylogenetic affiliation of PC and its relationship with myeloid DC remain controversial. Here we show that CD123(bright)HLA-DR(+) PC from FL-treated healthy volunteers can be divided into mutually exclusive subsets that harbor either lymphoid or myeloid features. Lymphoid-like PC represent the majority of PC and include pTalpha-, CD3epsilon-, and CD7-expressing cells. They exhibit TCR-beta gene loci in germline configuration and show low allostimulatory capacity, but produce type I IFN upon virus infection and can be differentiated in vitro into potent APC. Myeloid-like PC represent a minor fraction of the total PC population. They exhibit a striking PC/myeloid DC intermediate phenotype (CD5(+)CD11c(low)CD45RA(low)CD45RO(-)CD101(+)), produce proinflammatory cytokines, and do not require in vitro maturation to act as potent APCs. We propose that, rather than forming a lineage, PC might represent a population of lymphoid cells undergoing an in vivo cell fate conversion from a lymphoid to a myeloid cell type.
authors.affiliation: Discovery Research, Immunex Corp., Seattle, WA 98101-2936, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: Anne-Renee
authors.initials: AR
authors.lastname: Van der Vuurst de Vries
authors.forename: Charles R
authors.initials: CR
authors.lastname: Maliszewski
authors.forename: Laurent
authors.initials: L
authors.lastname: Galibert
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000096:biosynthesis; D001772:Blood Cell Count; D017252:CD3 Complex / Q000096:biosynthesis; D023201:CD40 Ligand / Q000494:pharmacology; D018956:CD5 Antigens / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005819:Genetic Markers; D006023:Glycoproteins / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D007370:Interferon Type I / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D053650:Interleukin-3 Receptor alpha Subunit; D015850:Interleukin-6 / Q000096:biosynthesis; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000008:administration & dosage; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis*
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; C419394:CD1b antigen; D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; C115335:CD3E protein, human; D018956:CD5 Antigens; D019002:CD56 Antigen; D005819:Genetic Markers; D006023:Glycoproteins; D006684:HLA-DR Antigens; C115022:IL3RA protein, human; D007370:Interferon Type I; D007375:Interleukin-1; D007377:Interleukin-3; D053650:Interleukin-3 Receptor alpha Subunit; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016185:Receptors, Interleukin-3; C084881:flt3 ligand protein; C090377:pre-T cell receptor alpha; D023201:CD40 Ligand