Plasmacytoid DCs (pDCs) are found mainly in the peripheral blood and bone marrow, and in the T cell areas of secondary lymphoid organs. pDCs are a specialized cell population that exhibit a plasma-cell like morphology and produce large amounts of type I IFN in response to viruses. These cells play a crucial role in the induction and maintenance of tolerance, properties that depend upon expression of the type I IFN receptor . pDCs are considered as an immature DC subtype able to differentiate in vitro into mature DCs, in response to different stimuli . In mice, pDCs express B220, Ly6C or CD11c but no CD123 (IL-3Rα) [30,31]. In humans, pDCs express CD4, CD123, HLA-DR, CD68, ILT-3 and CD45RA but lack CD11c, ILT-1, CD3, CD14, CD16, CD19, CD20 and CD56 [32,33]. Blood DC antigen (BDCA)-2 (CD303) and BDCA-4 (identical to neuropilin-1) are also human pDC-specific markers in the blood . BDCA-2 is a type II lectin C  that plays a role in antigen internalization and presentation as well as in the synthesis of IL-12. In the presence of IL-3, CD40L or viruses, pDC can differentiate into mature DCs. This process involves up-regulation of MHC class II, co-stimulatory molecules and the chemokine receptor CCR7, as well as the production of IL-12, and leads in turn to an enhancement of T lymphocyte activation [29,30,35]. Activated pDCs are able to produce a large variety of proimmune cytokines including IFN-α/β, granulocyte–macrophage colony-stimulating factor, TNF-α, IL-6 and IL-8 . In addition, human as well as murine mature pDCs affect T cells functions, leading to earlier activation, prolonged survival, IFN-γ production and Th1 differentiation, via different molecular mechanisms . In contrast, in humans and mice, freshly isolated immature pDCs express low levels of MHC class II and co-stimulatory molecules and are consequently very limited in their capacity to present antigen to T lymphocytes and to induce cytokine polarization [29,38]. In vivo, the tolerogenic potential of pDCs was demonstrated initially following the administration of murine liver pDCs in a cardiac allograft model . The latter cells were shown to acquire alloantigens in the allograft and then home, via the blood, to peripheral lymph nodes where they induced the generation of CD4+CD25+forkhead box P3 (FoxP3)+ Treg expressing chemokine (C-C motif) receptor 4 (CCR4) . Stimulation of pDCs with CD200-Ig , CTLA-4-Ig or glucocorticoid-induced TNF receptor family-related gene-Ig-induced IDO production and contributed to the tolerogenic state of these cells . Furthermore, pDCs from tumour-draining lymph nodes express IDO constitutively, suggesting that they help to maintain the state of immunosuppression within the tumour .
CD19+ DCs also have a plasma cell-like morphology, but unlike pDC they are found in the red pulp of the mouse spleen. These cells are normally capable of stimulating T cells. However, they can synthesize large amounts of IDO after ligation of CD80/86 by CTLA-4 bound on the surface of Treg or by ligation of Toll-like receptor 9 (TLR-9) , and thereby become immunosuppressive. As for pDC, the suppressive action of CD19+ DCs is under the control of type I IFN.