2 main DC subsets include pDC (CD11c+B220+) and myeloid DC (CD11c+CD11b+).

Markers:

Mouse pDCs CD45R (B220), CD8a

Human pDCs express CD45RA

CD11c-CD123+ plasmacytoid DCs (PDCs) are though to share precursor cells with lymphocytes. pDCs possess only a modest capacity to activate naive T cells and constitute an essential component of innate immunity be secreting various cytokines and chemokines as well as by participating in the activation of natural killer cells. Indeed, pDCs are considered to be a subset of immature DCs that specialize in the secretion of prodigious amounts of type I interferon (IFN) on stimulation by several viruses.

In contrast to myeloid DCs which express the myeloid marker CD11b, pDCs do not express DC11b, but instead express the CD45 isoform (B220) that is normally expressed by B cells.

Common lymphoid progenitor cells give rise to plasmacytoid precursor cells (pDC) which do not express CD11c but rather IL-3 receptor (CD123). Plasmacytoid DC (PDC) are major producers of type I IFN and IL-12, following TLR-mediated recognition of microbial factors, such as CpG DNA and thus likely play an important role during virus as well as bacterial and protozon infection. Plasmacytoid DCs, in fact, have been called “natural IFN-producing cells” because they secrete very large amount of IFN-??. 

Functions of Plasmacytoid DCs

• immature pDCs produce IFNa: PDCs produce IFN-alpha. PDC can produce up to 100 times more IFNalpha than other cell types. However, mature pDC lack the ability to produce IFNa. Compare mDCs which produce IL-12.

pDC secrete so much IFNa due to their interferon regulatory factor (IRF) 7 and 3 which transcribe IFNa genes. pDC can secrete IFNa without the need for feed-back signaling through the recetpor due to their constitutive expression of IRF7.

Addition of anti-TNFa antibodies maintain pDC at an immature state and maintains IFNy production. This could be important in cancer treatment since if you can maintain pDCs at immature state, this could lead to higher IFNy production.

• Immunostimulatory functions: PDCs are also involved in activation of macrophages and NK cells, and, through IL-15 production, they enhance the proliferation of CD8+ T lymphocytes.

In contrast to M-DCs, circulating human PDCs produce low amounts of CCR4, CCL17 and CCL22.

• pDC lack phagocytic capacity

• Whereas mDCs are potent antigen-representing cells and are typically associated with T cell activation and the initiation of an adaptive immune response, pDCs possess only a modest capacity to activate naive T cells.

• pDCs constitute an essential component of innate immunity be secreting various cytokines and chemokines as well as by participating in the activation of natural killer cells. Indeed, pDCs are considered to be a subset of immature DCs that specialize in the secretion of prodigious amounts of T ype IFN on stimulation be several viruses.

• When stimulated pDCs enter lymph nodes via the blood. Comapre myDC which enter the lumph nodes via afferent lymphatics. Migration is controlled by chemokines.

• pDC may induce immune tolerance: They have been shown to produce T-reg cells. They can induce CD4+ T cells to produce IL-10. They may also promote CD8+ T cells to produce IL-10 and IFNy. Immature donor DC can prolong donor specific graft survival by subversion/suppression/dampening of recipient T cell responses to alloantigen, but the mechanism is not clear. For example, in mice pDC potentiates the survival of heart allografts.

Development

Flt3l results in markedly increased number of pDCs. It is a critical growth factor for the development of pDC.

Immature pDCs do not look like DCs at all.

PDCs in Disease:

HIV: HIV infected long term non progressors (LTNPs) are characterized by an increased number and function of PDC. PDC express both the primary receptor (CD4) and the entry co-receptors (CSCR4, CCR5) for HIV, although viral replication in these cells in vitro is very inefficient.

Psoriasis: pDCs may play a role in the pathogenesis of psoriasis which is one of the most common T-cell mediated autoimmune disease of the skin. If you treat patients with IFNa, one exacerbates the disease. It is beleive pDCs infiltrate skin which activates IFNa which activates myDCs which produce IL-12, IL-23 and TNFa which stimulate T cells which produce IFNy.

Multiple sclerosis/EAE: EAE exacerbated in IFN B -/- mice.