Plasmacytoid dendritic cells (pDCs) are one of two principal subsets of human dendritic cells (DCs). pDCs were initially identified in pathological specimens of reactive or neoplastic lymph nodes (LNs), in close association with high endothelial venules (HEVs)(44). Their plasma cell-like morphology and localization led to their designation as “plasmacytoid T cells,” or “plasmacytoid monocytes”(reviewed in reference 31). Subsequently, these cells were found to correspond to a subset of circulating blood DCs, an immature CD11cJ population, now referred to as pre-pDCs (an immediate precursor of pDCs), and to be distinct from “conventional” myeloid CD11c+ DCs (mDCs)(60). Pre-pDCs express CD4 but lack T-cell receptor alpha (TCRɑ), TCRβ, TCRγ, TCRδ, or CD3 chains. Furthermore, they do not express B-cell lineage (CD19, CD21) or myeloid (CD13, CD14, CD33) markers. Pre-pDCs typically mature and produce large amounts of alpha/beta interferons (IFN-ɑ/β) in response to viral and bacterial stimuli (76). This property further identified them as the enigmatic “natural type I IFN-producing cell” in blood (25, 51, 131), a rare CD4+, MHC class II+ cell with potential to secrete significant amounts of IFN-ɑ (1, 29, 48). pDCs display an antigen-presenting function, thereby firmly establishing them as members of the DC family. While mDCs comprise several subsets of DCs, including Langerhans cells (LCs), dermal dendritic cells, and interstitial DCs, pDCs have not yet been segregated into subpopulations.

Recently, several groups simultaneously identified the murine pDC equivalent as a CD11c lo-int, B220+, IFN-ɑ/β-producing cell in spleen, LNs, thymus (7, 17, 105, 109), and blood (110). Murine pDCs differ from their human counterparts in expressing low to intermediate levels of CD11c, with lymphoid tissue pDCs also expressing CD4 and/or CD8ɑ. Furthermore, murine pDCs from the spleen, but not blood, secrete interleukin-12 (IL-12)(p70) after stimulation with Staphylococcus aureus Cowan (SAC), in contrast to human pDCs (17).