Monocytes and cells of the dendritic cell lineage circulate in blood and eventually migrate into tissue where they further mature and serve various functions, most notably in immune defense. Over recent years these cells have been characterized in detail with the use of cell surface markers and flow cytometry, and subpopulations have been described. The present document proposes a nomenclature for these cells and defines 3 types of monocytes (classical, intermediate, and nonclassical monocytes) and 3 types of dendritic cells (plasmacytoid and 2 types of myeloid dendritic cells) in human and in mouse blood. This classification has been approved by the Nomenclature Committee of the International Union of Immunological Societies, and we are convinced that it will facilitate communication among experts and in the wider scientific community.

Limited response to idiotype vaccination in patients with myeloma suggests that there is a need to develop better immunotherapy strategies. It has been determined that the number of high-potency CMRF44 ؉ CD14 ؊ CD19 ؊ dendritic cells (DCs) in the blood of patients with myeloma (range, 0.03%-0.8% of mononuclear cells [MNCs]; n ‫؍‬ 26) was not significantly different from that in controls (range, 0.05%-0.8% of MNCs; n ‫؍‬ 13). Expression of the costimulatory molecules CD80 and CD86 on DCs from these patients (mean, 29%؎17% of MNCs and 85%؎10% of MNCs, respectively) was also normal (mean, 29%؎17% and 86%؎16% of MNCs, respectively). Up-regulation of CD80 expression in response to stimulation by human (hu)CD40LT ؉ interleukin (IL)-2 was significantly reduced on the DCs of patients with myeloma during stable disease (n ‫؍‬ 9) and was absent during progressive stages (n ‫؍‬ 7) of disease. Similar effects were seen on B cells but not on monocytes of the same group of patients. CD86 expression on DCs was high before (86%) and after (89%)

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DEC-205 (CD205) belongs to the macrophage mannose receptor family of C-type lectin endocytic receptors and behaves as an antigen uptake/processing receptor for dendritic cells (DC). To investigate DEC-205 tissue distribution in human leukocytes, we generated a series of anti-human DEC-205 monoclonal antibodies (MMRI-5, 6 and 7), which recognized epitopes within the C-type lectin-like domains 1 and 2, and the MMRI-7 immunoprecipitated a single approximately 200 kDa band, identified as DEC-205 by mass spectrometry. MMRI-7 and another DEC-205 mAb (MG38), which recognized the epitope within the DEC-205 cysteine-rich and fibronectin type II domain, were used to examine DEC-205 expression by human leukocytes. Unlike mouse DEC-205, which is reported to have predominant expression on DC, human DEC-205 was detected by flow cytometry at relatively high levels on myeloid blood DC and monocytes, at moderate levels on B lymphocytes and at low levels on NK cells, plasmacytoid blood DC and T lymphocytes. MMRI-7 F(ab')2 also labeled monocytes, B lymphocytes and NK cells similarly excluding reactivity due to non-specific binding of the mAb to FcgammaR. Tonsil mononuclear cells showed a similar distribution of DEC-205 staining on the leukocytes. DEC-205-specific semiquantitative immunoprecipitation/western blot and quantitative reverse transcriptase-PCR analysis established that these leukocyte populations expressed DEC-205 protein and the cognate mRNA. Thus, human DEC-205 is expressed on more leukocyte populations than that were previously assumed based on mouse DEC-205 tissue localization studies. The broader DEC-205 tissue expression in man is relevant to clinical DC targeting strategies and DEC-205 functional studies.

+subsets that display unique gene expression profiles, suggesting specialized functions. CD1c+ DCs express TLR4 while CD141 + DCs do not, thus predicting that these two subsets have differential capacities to respond to Escherichia coli. We isolated highly purified CD1c + and CD141 + DCs and compared them to in vitro generated monocyte-derived DCs (MoDCs) following stimulation with whole E. coli. As expected, MoDCs produced high levels of the proinflammatory cytokines TNF, IL-6, and IL-12, were potent inducers of Th1 responses, and processed E. coli-derived Ag. In contrast, CD1c + DCs produced only low levels of TNF, IL-6, and IL-12 and instead produced high levels of the anti-inflammatory cytokine IL-10 and regulatory molecules IDO and soluble CD25. Moreover, E. coli-activated CD1c + DCs suppressed T-cell proliferation in an IL-10-dependent manner. Contrary to their mouse CD8 + DC counterparts, human CD141 + DCs did not phagocytose or process E. coli-derived Ag and failed to secrete cytokines in response to E. coli. These data demonstrate substantial differences in the nature of the response of human blood DC subsets to E. coli. Keywords: E. coli r Human dendritic cells r IL-10 See accompanying Commentary by Qian and CaoSupporting Information available online IntroductionDCs are potent antigen-presenting cells that play a fundamental role in the induction and regulation of innate and adaptiveCorrespondence: Dr. Kristen J. Radford e-mail: kradford@mmri.mater.org.au immune responses against microbial pathogens. DCs detect microbial products using a sophisticated repertoire of PRR that include the toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors, retinoic acid * These authors contributed equally to this work.C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2012. 42: 1512-1522 Immunity to infection 1513 inducible gene 1 (RIG-I)-like receptors and C-type lectins. The nature of the immune response to a given pathogen is tightly regulated by the DC network, which consists of multiple subsets that are equipped with unique PRRs and are endowed with specialized functions. DCs in humans and mice can be categorized into three broad subtypes. These three subtypes are: (i) inflammatory DCs that are mobilized rapidly from monocytes in response to infection and inflammation (monocyte-derived DCs; MoDCs), (ii) migratory DCs that reside in the peripheral tissues and migrate to lymphoid tissues after encounter with Ag, and (iii) the blood and lymphoid tissue resident DCs that are comprised of plasmacytoid and myeloid DCs [1]. Further complexity arises within the steadystate myeloid DC subsets, which in humans are defined as lineage (CD3,14,15,19,20,56 ResultsMoDCs are the main DC subset responsive to E. coli CD1c + and CD141 + DCs were enriched from healthy donor leukapheresis products by immuno-magnetic selection, and flow sorted to high purity (>99%) using our established human DC isolation protocols [8,19]. Autologous MoDCs were differentiated from...