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CD123^bright Plasmacytoid Predendritic Cells: Progenitors Undergoing Cell Fate Conversion?

Discovery Research, Immunex Corp., Seattle, WA 98101

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^brightHLA-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 pT-, CD3-, and CD7-expressing cells. They exhibit TCR- 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^lowCD45RA^lowCD45RO^-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.

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