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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-03-0974.
IMMUNOBIOLOGY
From the Walter and Eliza Hall Institute of Medical
Research, Melbourne, Australia; Institute of Medical
Microbiology, Immunology and Hygiene, Technical University of Munich,
Germany; Monash Institute of Reproduction and Development,
Clayton, Australia; and Department of Veterinary Science,
University of Melbourne, Australia.
Immature and predendritic cells (pre-DCs) of human blood are
the most readily accessible human DC sources available for study ex
vivo. Murine homologues of human blood DCs have not been described. We
report the isolation and characterization of 2 populations of precursor
DCs in mouse blood. Mouse blood cells with the surface phenotype
CD11cloCD11b In 1992, Inaba et al1 identified
proliferating cells in mouse blood that differentiated into dendritic
cells (DCs) after 7-day culture in granulocyte
macrophage-colony-stimulating factor (GM-CSF). Soon after, 2 groups2,3 identified monocytelike DC precursors (pre-DCs)
in human blood. The DCs generated in vitro from human blood monocytes
after 7 days under the influence of GM-CSF and interleukin-4 (IL-4),
followed by a maturation stimulus such as tumor necrosis factor- Another distinct DC lineage cell found in human blood is the
CD11c In contrast to these studies on human blood, little attention has been
paid to the DC-lineage cells of mouse blood since the pioneering work
of Inaba et al.1,19 Instead, most information on murine
DCs derives from their direct isolation, in a relatively mature form,
from lymphoid tissues. Multiple subtypes of mature mouse DCs have been
described.20-22 However, the relationship of these
directly isolated mouse DCs to human DCs generated from blood
precursors in culture is unclear, and it has been argued that the
products of human blood pre-DC1 and pre-DC2 are normally only produced
on microbial stimulation and that their equivalents might not be
represented among the DCs of uninfected laboratory mice.6
However, in one case in which mature DCs were directly isolated using
similar procedures from human thymus and mouse thymus, there was a
close correlation of most surface markers and of cytokine production
potential; an exception was CD8 Accordingly, to provide a direct comparison with the human DC
system, it was important to isolate and characterize the immediate DC
precursors of mature DCs from mouse blood, despite the inconvenience and expense of this source. In the present study we have identified 2 populations in mouse blood that appear to be the equivalents of those
in human blood. A CD11c+ iDC population is described that
expresses myeloid markers and produces CD8 Mice
Immunofluorescence labeling of DCs
For surface phenotype analyses, the following mAb conjugates were used:
anti-CD11c (N418)-Cy5 or FITC, anti-major histocompatibility complex
(MHC) class 2 (N22 or M5/114)-FITC or Alexa 594 (the conjugation levels were deliberately less than maximal to ensure the strong staining for MHC class 2 on DCs at saturation did not cause inaccurate color compensation problems in other channels), anti-CD8 FACS analysis and sorting of DC populations For sorting DC and pre-DC populations, a MoFlo instrument (Cytomation, Fort Collins, CO) was used. Reanalysis was routinely performed, and populations were only used for further functional analyses when the purity was greater than 95%. Most analyses were performed on a FACStar Plus instrument (Becton Dickinson, San Jose, CA), as previously described,20 using up to 4 fluorescence channels for immunofluorescence staining (FL1 for FITC, FL2 for PE, FL3 for Cy5, and FL4 for Alexa 594), with the FL5 channel set to exclude PI-positive dead cells and autofluorescence cells. Care was taken during gating that any cells brightly fluorescent in FL3 and spilling over into FL5 were not gated out as dead cells.Preparation of mouse spleen DCs Spleen DCs were isolated exactly as described elsewhere.20Preparation of pre-DCs from mouse blood Mouse blood was collected from 20 to 50 mice through cardiac puncture into heparinized glass tubes. The blood was diluted 1:3 with a mouse osmolarity salt solution lacking divalent ions and containing 5 mM EDTA (ethylenediaminetetraacetic acid)-balanced salt solution (EDTA/BSS).23 Diluted blood samples were layered over Lympholyte M (density, 1.0875 ± 0.0005 g/cm3; Cedarlane Laboratories, Ontario, QC, Canada) and centrifuged at room temperature (RT) according to the manufacturer's instructions. The peripheral blood mononuclear cell (PBMC) fraction was then removed, washed in EDTA/BSS, and resuspended in Nycodenz medium (1.086 g/cm3 at 4°C) mouse osmolarity (analytical grade powder; Nycomed Pharma AS, Oslo, Norway; made iso-osmotic in water, then diluted in EDTA/BSS). Cells suspended in Nycodenz medium were layered on an equal volume of Nycodenz medium and were subjected to further density separation (1700g, 15 minutes, 4°C) to further enrich the sample for DCs and pre-DCs. The light density cell fraction (now only approximately 30% of the PBMCs that were recovered from Lympholyte) was washed in EDTA/BSS, pelleted, and then incubated with a cocktail of optimally titrated monoclonal antibodies to deplete the preparation of CD19+ B cells (mAb, ID3), T cells (mAb, KT3-1.1), granulocytes (mAb, RB68C5), and residual red blood cells (mAb, TER-119). Cells binding mAb were depleted by antirat immunoglobulin magnetic beads (Dynabeads; Dynal, Oslo, Norway), as previously described for the purification of splenic DCs.20 Approximately 50% of the resultant cells were either autofluorescent and had extremely high side scatter (these cells were most prevalent in male mice) or were positive for the pan-NK cell marker, DX5; neither of these cells included immediate precursors of DCs (data not shown). The antibody-depleted preparation was, therefore, labeled with DX5-biotin and streptavidin-Cy5 and DX5-positive cells and cells autofluorescent in the FITC and PE channels. Cells autofluorescent in the FITC and PE channels were eliminated by fast presorting on the MoFlo instrument, with the nonfluorescent cells providing a highly enriched source of pre-DCs. For final purification of pre-DC subtypes, the presorted cells were labeled with anti-CD11c-FITC and anti-CD45RA, and the 2 distinct CD11cloCD45Rahi and CD11cintCD45RA populations were sorted using
the MoFlo instrument. The procedure is summarized in the flow chart of
Figure 1.
Electron microscopy Cell pellets were fixed in 2.5% glutaraldehyde in phosphate-buffered saline (PBS) at 4°C overnight, washed in PBS, and postfixed in 1% osmium tetroxide in PBS for 1 hour. After they were washed in distilled water, the cell pellets were dehydrated in acetone and embedded in Procure-Araldite resin (ProSciTech; Thuringowa, Australia). During dehydration, the cells were stained en block with 2% uranyl acetate in 70% acetone. Semithin (1 µm) sections were cut through the maximum thickness of each pellet and stained with a solution of 1% methylene blue and 1% sodium tetraborate. Ultrathin sections were stained with a 5% aqueous solution of uranyl acetate for 10 minutes, washed with distilled water, and stained with Reynold lead citrate for 10 minutes. After staining, the sections were examined by a Philips 300 electron microscope operated at 60 kV.Cytokines and stimulants of pre-DCs Murine recombinant granulocyte macrophage-colony-stimulating factor (GM-CSF; used at 200 U/mL), murine recombinant interleukin-3 (rIL-3; used at 100 U/mL), murine recombinant tumor necrosis factor- (rTNF-; used at 100 U/mL), and murine rIL-4 (used at 100 U/mL) were
gifts from Immunex (Seattle, WA). Recombinant rat IFN- (used at 20 ng/mL and bioactive with mouse cells) was purchased from PeproTech
(Rocky Hill, NJ). Murine rIL-12 p70 was purchased from R&D Systems
(Minneapolis, MN). Oligonucleotides containing a fully phosphorothioated CpG motif were synthesized by GeneWorks
(Adelaide, Australia) according to a published sequence
(CpG1668)24 and were used at 200 nM.
Differentiation and activation of pre-DCs in culture The pre-DCs were incubated at 0.5 × 106 or 0.25 × 106 cells/mL in U-bottom wells of 96-well tissue-culture plates in a humidified 10% CO2 in air incubator at 37°C for 8 to 36 hours. Modified mouse osmolarity RPMI 1640 medium25 was used, together with the appropriate cytokines and stimulants.Quantitation of cytokine production Analysis of IL-12 production in culture supernatants was carried out using enzyme-linked immunosorbent assay (ELISA), as previously described.26,27A bioassay for type 1 IFN was performed as described
previously.26 In addition, IFN- MLR cultures for T-cell stimulation capacity CD4+ T cells were purified from pooled mesenteric, axillary, brachial, and inguinal lymph nodes of CBA/CaH mice as previously described.28 Pre-DC subpopulations, isolated and sorted as described above, were first cultured overnight as above in their own optimal stimulating medium CD11cloCD45RAhi in 200 U/mL GM-CSF, 200 nM CpG or CD11cintCD45RA in 200 U/mL GM-CSF,
and 100 U/mL TNF-and in the optimal stimulating medium of the
other population. Cultured pre-DCs were washed 3 times with EDTA/BSS
containing 2% fetal calf serum (FCS), and the number of viable cells
was determined. Freshly isolated or viable precultured pre-DCs
(1 × 103) were added to U-bottom wells containing
20 × 103 T cells. All cells were suspended and cultured
in modified RPMI 1640 medium described in "Preparation of pre-DCs
from mouse blood." Total culture volume was 100 µL.
Replicate culture trays were incubated at 37°C in 10%
CO2 in air for 3 to 6 days. At days 3, 4, 5, and 6, a
culture tray was pulsed with 3H-thymidine, 1 µCi (0.037 MBq)/well, for 6 hours, then frozen. Trays were thawed, cells
were harvested onto glass fiber filters, and thymidine incorporated was
counted by liquid scintillation. All cultures at all times were grown
at least in triplicate, and background controls, with T cells or
pre-DCs only, were included at each time point.
Low levels of mature DCs in mouse blood Analysis of mouse blood PBMC preparations or of further enrichment stages revealed only extremely low levels of cells with a surface phenotype approaching that of the mature DCs found in lymphoid organs (MHC class 2hi, CD11c+). The numbers of these relatively mature DCs detected varied between preparations, but indications were that there were fewer than 1000 cells of near-mature phenotype in the blood of one mouse. The few that were detected were mainly CD11b+CD8.
Detection and enrichment of pre-DCs in mouse blood In view of the paucity of mature DCs, we tested whether mouse blood, like human blood, contained earlier stages of DC development. PBMCs from mouse blood were segregated in various ways, then tested for their ability to produce mature DCs in short-term culture. A range of cytokine and bacterial stimuli combinations was tested for the up-regulation of MHC class 2 and CD11c and for the acquisition of typical DC morphology. Precursors of such putative mature DCs were present in the PBMC fraction and were enriched in among the lighter density cells. However, they were absent from the PBMC fractions positive for certain markers of B cells (CD19), T cells (CD3), and erythroid cells. They were also absent from cells expressing very high levels of the myeloid markers CD11b and GR-1, which were extremely adherent or granular in appearance.A large group of PBMCs coexpressed intermediate levels of DX5 and CD11c but, on culture, down-regulated CD11c and did not express MHC class 2 or acquire DC morphology; thus, it appeared these were NK-lineage cells and not pre-DCs. A large but variable group of autofluorescent cells, which had the potential to contaminate subsequent immunofluorescence sorting, was also found not to include pre-DCs. By positively selecting for the lighter density cells and excluding, by depletion and presorting steps, these inactive populations of lineage-positive or autofluorescent cells, the scheme of Figure 1 was devised to provide a highly enriched source of pre-DCs. Two populations of pre-DCs in mouse blood Two distinct populations of pre-DCs, both able to rapidly differentiate into DCs in culture, were discovered. These were cells of the phenotypes CD11cintCD45RACD11b+ and
CD11cloCD45RA+CD11b (Figure
2), and they represented 35% and
10%, respectively, of the enriched pre-DC population or 0.07% and
0.025%, respectively, of mouse PBMCs. Both populations were
medium-sized cells with medium-high forward and low side light-scatter
profiles. Their surface phenotype, as freshly isolated, is shown in
Figure 2.
Most cells in both blood pre-DC cell populations expressed extremely
low levels of MHC class 2, low levels of CD40, and undetectable levels
of CD80 and CD86. The only exception to this was a small subgroup of
cells within the
CD11cintCD45RA
Maturation of CD11cintCD45RA population
up-regulated surface MHC class 2 and acquired DC morphology after as
little as 8 hours culture, even in the absence of exogenous cytokines
in the media (data not shown). Under these conditions, however, cell
viability was poor. The presence of GM-CSF improved the overall
recovery of viable cells to approximately 70% after overnight culture,
and the additional presence of TNF- produced maximal expression of MHC class 2 and CD40. However, the cells did not express CD4 or CD8,
even if cultured in the presence of CpG. At this time, the cultured
products of CD45RAhiCD11clo precursors closely
resembled CD4CD8 DCs isolated from mouse
spleen and cultured for the same time period (data not shown). After 36 hours of culture, cell viability had dropped to 30% to 40%, but the
remaining viable cells were all large cells with DC morphology,
expressing high levels of CD11c and MHC class 2 (Figure
4A). At this time approximately 10% of
the cells showed low staining for CD8, though most remained CD8 and all remained CD4.
Functional maturation was checked by the ability to stimulate
allogeneic mouse T cells in MLR culture. Freshly isolated
CD45RAhiCD11clo pre-DCs did not efficiently
stimulate the allogeneic T cells, even after 6 days of coculture,
provided the small group of CD11chi near-mature DCs was
gated out during sorting. However, if the CD11cintCD45RA
Maturation of CD11cloCD45RAhi blood pre-DCs in culture When cultured in medium without exogenous cytokines, the CD11cloCD45RA+ population died rapidly without maturation. In contrast to the CD11cintCD45RA
cells, the CD11cloCD45RAhi population did not
respond by maturation to the GM-CSF/TNF- combination; instead it
died rapidly. GM-CSF alone improved viability but did not induce
maturation or proliferation. However, if CpG was used as a stimulus,
together with GM-CSF, IL-3, or both, rapid differentiation to cells
that resembled mature DCs was observed. The optimal time for mature DC
production was 36 hours, when the cells had increased in size,
developed dendrites, and displayed higher forward and side scatter. The
overall recovery of viable cells at this time was 80%. CpG induced the
up-regulation of MHC class 2 and CD11c (Figure 4B). In contrast to the
reports for human CD11c pre-DCs, mouse
CD11cloCD45RA+ pre-DCs did not acquire DC
phenotype or morphology in the presence of IL-3, or IL-3 plus GM-CSF,
unless an additional microbial-derived stimulus was present. CpG also
induced the expression of the high levels of CD8 on approximately
50% of the cells, but only marginal staining for CD4 was obtained.
Functional testing in the MLR system revealed that freshly isolated
CD11cloCD45RA+ did not induce proliferation by
naive allogeneic T cells. However, preincubation overnight with CpG and
GM-CSF to produce a DC morphology and phenotype produced cells able to
stimulate T cells (Figure 5). Stimulator capacity was less than that of
the DCs produced by the CD11cintCD45RA Cytokine production by mouse blood pre-DCs Analysis of mouse blood pre-DCs revealed similarities between the murine CD11cintCD45RA population and human
blood pre-DC1 monocyte precursors of human "myeloid" DC1 and
between the murine CD11cloCD45RA+ population
and human blood plasmacytoid pre-DC2. To further check these
similarities, we examined their capacity to produce 2 key cytokines,
type 1 IFN and IL-12 p70. Production of type 1 IFN is a hallmark of the
plasmacytoid human pre-DC2.16,18 Human pre-DC1 have
been reported to produce bioactive IL-12 p70 and to induce
TH1 responses29; however, in apparent
contradiction to this, it is the murine CD8+ DCs that are
the major IL-12 p70 producers among murine splenic DCs.26,30
Freshly isolated mouse blood pre-DCs were separated, sorted into the 2 subtypes, and stimulated in culture with CpG, an effective inducer of
type 1 IFN. Type 1 IFNs were detected in the supernatants of
CD11cloCD45RAhi pre-DCs, but not in the
supernatants of CD11cintCD45RA
Mouse blood pre-DCs were also tested for the production of IL-12 in
response to CpG and the mixture of cytokines previously shown to lead
to optimal production of the bioactive form of this cytokine.27 The response was compared with that of freshly
isolated splenic CD11c+ DCs. The
CD11cintCD45RA
We have identified 2 major populations of pre-DCs in mouse blood, together with a minor group of immature DCs. This allows, for the first time, a direct comparison of the DC-lineage cells in human and mouse blood. It is now clear that similar populations of pre-DCs are found circulating in both species and that they have similar biologic functions. The CD11cintCD45RA The CD11cloCD45RA+ pre-DC subset of mouse blood
is clearly analogous to the human plasmacytoid pre-DC2 subset. The lack
of myeloid markers, the morphology, the differentiation into mature DCs
under the influence of IL-3 and CpG rather than GM-CSF and TNF- There are some differences between mouse blood plasmacytoid pre-DCs and human blood plasmacytoid pre-DCs, but the apparent species differences diminish if mouse lymphoid tissue plasmacytoid pre-DCs are included in the comparison. We and others33-36 have analyzed the plasmacytoid pre-DCs from mouse spleen, thymus, and lymph nodes, and their basic properties and surface phenotype are similar to those in mouse blood. Both are CD45RAhiCD11clow/int, and both produce type 1 IFN and transform into CD8+ DCs when stimulated by CpG. However, many of the mouse lymphoid tissue forms of this cell, in contrast to those in blood, express CD4 and low levels of IL-3R. Many of the mouse lymphoid tissue forms are, therefore, closer to human plasmacytoid pre-DCs, which express CD4 and IL-3R. However, apart from CD4, many lymphoid tissue plasmacytoid pre-DCs also express CD8, a molecule not found on the surfaces of human or mouse plasmacytoid pre-DCs. It is of note that the human blood pre-DC populations appear to express comparatively higher levels of MHC class 2 than the mouse blood pre-DCs we have isolated. In addition, human blood pre-DC2 cells do not require an added microbial stimulus, such as CpG, for DC differentiation in the presence of IL-3; they also express higher levels of IL-3R. Furthermore, there are several reports of a low-level T-cell stimulation by human blood pre-DCs, particularly pre-DC1,37,38 whereas the mouse pre-DC subsets we have isolated require maturation in culture before detectable T cell stimulation is observed in MLR. We have also found that lymphoid tissue plasmacytoid pre-DCs require activation by bacterial products before they can induce the stimulation of allogeneic T cells in MLR.36 All this suggests that human blood pre-DCs are slightly more mature or activated than are mouse pre-DC subsets. This may be a species difference, but it might also indicate a difference between the pathogen-free environment of our laboratory mice compared with a level of exposure to microbial stimuli for the human blood donors. The relationship between the pre-DC populations we have found in
mouse blood and the mature DC subtypes in mouse lymphoid tissue must
now be considered. The
CD11cintCD45RA The large number of mice required makes extensive precursor-product studies on mouse blood pre-DCs an impractical enterprise. Our expensive and tedious studies on mouse blood have, however, served the purpose of demonstrating the close relationship of the DC systems of the 2 species, provided the same source material and similar direct isolation procedures are used in the investigation. Treating mice with DC poietins, such as Flt3-L, may prove to be a useful technique to further study the pre-DCs of mouse blood using fewer mice. Apart from increasing DC numbers, treatments with cytokines such as Flt3-L do alter some of the biologic properties of DCs28 and so it is necessary that the basic properties of pre-DCs in the normal mouse be understood first. We and others33,35,36 have found a more plentiful source of mouse plasmacytoid pre-DCs in bone marrow, thymus, spleen, and lymph nodes. We are currently using these sources in more direct studies of DC precursors to DC product relationships in vivo.
Submitted April 26, 2002; accepted September 22, 2002.
Prepublished online as Blood First Edition Paper, October 10, 2002; DOI 10.1182/blood-2002-03-0974.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Meredith O'Keeffe, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia; e-mail: okeeffe{at}wehi.edu.au.
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© 2003 by The American Society of Hematology.
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  M. L. Salem, C. M. Diaz-Montero, A. A. Al-Khami, S. A. El-Naggar, O. Naga, A. J. Montero, A. Khafagy, and D. J. Cole Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C) J. Immunol., February 15, 2009; 182(4): 2030 - 2040. [Abstract] [Full Text] [PDF]
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 N. Zucchini, G. Bessou, S. H. Robbins, L. Chasson, A. Raper, P. R. Crocker, and M. Dalod Individual plasmacytoid dendritic cells are major contributors to the production of multiple innate cytokines in an organ-specific manner during viral infection Int. Immunol., January 1, 2008; 20(1): 45 - 56. [Abstract] [Full Text] [PDF]
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 I. Caminschi, F. Ahmet, K. Heger, J. Brady, S. L. Nutt, D. Vremec, S. Pietersz, M. H. Lahoud, L. Schofield, D. S. Hansen, et al. Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells J. Exp. Med., October 29, 2007; 204(11): 2579 - 2590. [Abstract] [Full Text] [PDF]
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A. Rydstrom and M. J. Wick Monocyte Recruitment, Activation, and Function in the Gut-Associated Lymphoid Tissue during Oral Salmonella Infection J. Immunol., May 1, 2007; 178(9): 5789 - 5801. [Abstract] [Full Text] [PDF]
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U. Yrlid, V. Cerovic, S. Milling, C. D. Jenkins, J. Zhang, P. R. Crocker, L. S. Klavinskis, and G. G. MacPherson Plasmacytoid Dendritic Cells Do Not Migrate in Intestinal or Hepatic Lymph J. Immunol., November 1, 2006; 177(9): 6115 - 6121. [Abstract] [Full Text] [PDF]
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J. Diao, E. Winter, C. Cantin, W. Chen, L. Xu, D. Kelvin, J. Phillips, and M. S. Cattral In Situ Replication of Immediate Dendritic Cell (DC) Precursors Contributes to Conventional DC Homeostasis in Lymphoid Tissue. J. Immunol., June 15, 2006; 176(12): 7196 - 7206. [Abstract] [Full Text] [PDF]
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U. Yrlid, S. W. F. Milling, J. L. Miller, S. Cartland, C. D. Jenkins, and G. G. MacPherson Regulation of Intestinal Dendritic Cell Migration and Activation by Plasmacytoid Dendritic Cells, TNF-{alpha} and Type 1 IFNs after Feeding a TLR7/8 Ligand J. Immunol., May 1, 2006; 176(9): 5205 - 5212. [Abstract] [Full Text] [PDF]
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J. Zhang, A. Raper, N. Sugita, R. Hingorani, M. Salio, M. J. Palmowski, V. Cerundolo, and P. R. Crocker Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors Blood, May 1, 2006; 107(9): 3600 - 3608. [Abstract] [Full Text] [PDF]
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G. S. Angelov, M. Tomkowiak, A. Marcais, Y. Leverrier, and J. Marvel Flt3 Ligand-Generated Murine Plasmacytoid and Conventional Dendritic Cells Differ in Their Capacity to Prime Naive CD8 T Cells and to Generate Memory Cells In Vivo J. Immunol., July 1, 2005; 175(1): 189 - 195. [Abstract] [Full Text] [PDF]
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G. T. Belz, K. Shortman, M. J. Bevan, and W. R. Heath CD8{alpha}+ Dendritic Cells Selectively Present MHC Class I-Restricted Noncytolytic Viral and Intracellular Bacterial Antigens In Vivo J. Immunol., July 1, 2005; 175(1): 196 - 200. [Abstract] [Full Text] [PDF]
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Y. Omatsu, T. Iyoda, Y. Kimura, A. Maki, M. Ishimori, N. Toyama-Sorimachi, and K. Inaba Development of Murine Plasmacytoid Dendritic Cells Defined by Increased Expression of an Inhibitory NK Receptor, Ly49Q J. Immunol., June 1, 2005; 174(11): 6657 - 6662. [Abstract] [Full Text] [PDF]
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G.-X. Yang, Z.-X. Lian, K. Kikuchi, Y.-J. Liu, A. A. Ansari, S. Ikehara, and M. E. Gershwin CD4- Plasmacytoid Dendritic Cells (pDCs) Migrate in Lymph Nodes by CpG Inoculation and Represent a Potent Functional Subset of pDCs J. Immunol., March 15, 2005; 174(6): 3197 - 3203. [Abstract] [Full Text] [PDF]
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M. O'Keeffe, T. C. Brodnicki, B. Fancke, D. Vremec, G. Morahan, E. Maraskovsky, R. Steptoe, L. C. Harrison, and K. Shortman Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development Int. Immunol., March 1, 2005; 17(3): 307 - 314. [Abstract] [Full Text] [PDF]
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K. McKenna, A.-S. Beignon, and N. Bhardwaj Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity J. Virol., January 1, 2005; 79(1): 17 - 27. [Full Text] [PDF]
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 L. M. Hengesbach and K. A. Hoag Physiological Concentrations of Retinoic Acid Favor Myeloid Dendritic Cell Development over Granulocyte Development in Cultures of Bone Marrow Cells from Mice J. Nutr., October 1, 2004; 134(10): 2653 - 2659. [Abstract] [Full Text] [PDF]
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 H. Hochrein, B. Schlatter, M. O'Keeffe, C. Wagner, F. Schmitz, M. Schiemann, S. Bauer, M. Suter, and H. Wagner Herpes simplex virus type-1 induces IFN-{alpha} production via Toll-like receptor 9-dependent and -independent pathways PNAS, August 3, 2004; 101(31): 11416 - 11421. [Abstract] [Full Text] [PDF]
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J. Diao, E. Winter, W. Chen, C. Cantin, and M. S. Cattral Characterization of Distinct Conventional and Plasmacytoid Dendritic Cell-Committed Precursors in Murine Bone Marrow J. Immunol., August 1, 2004; 173(3): 1826 - 1833. [Abstract] [Full Text] [PDF]
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H. Yoneyama, K. Matsuno, Y. Zhang, T. Nishiwaki, M. Kitabatake, S. Ueha, S. Narumi, S. Morikawa, T. Ezaki, B. Lu, et al. Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules Int. Immunol., July 1, 2004; 16(7): 915 - 928. [Abstract] [Full Text] [PDF]
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G. T. Belz, C. M. Smith, L. Kleinert, P. Reading, A. Brooks, K. Shortman, F. R. Carbone, and W. R. Heath Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus PNAS, June 8, 2004; 101(23): 8670 - 8675. [Abstract] [Full Text] [PDF]
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M. Franchini, H. Hefti, S. Vollstedt, B. Glanzmann, M. Riesen, M. Ackermann, P. Chaplin, K. Shortman, and M. Suter Dendritic Cells from Mice Neonatally Vaccinated with Modified Vaccinia Virus Ankara Transfer Resistance against Herpes Simplex Virus Type I to Naive One-Week-Old Mice J. Immunol., May 15, 2004; 172(10): 6304 - 6312. [Abstract] [Full Text] [PDF]
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 H. C. O'Neill and H. L. Wilson Limitations with in vitro production of dendritic cells using cytokines J. Leukoc. Biol., April 1, 2004; 75(4): 600 - 603. [Abstract] [Full Text] [PDF]
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C. Sunderkotter, T. Nikolic, M. J. Dillon, N. van Rooijen, M. Stehling, D. A. Drevets, and P. J. M. Leenen Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response J. Immunol., April 1, 2004; 172(7): 4410 - 4417. [Abstract] [Full Text] [PDF]
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M. Salio, M. J. Palmowski, A. Atzberger, I. F. Hermans, and V. Cerundolo CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens J. Exp. Med., February 17, 2004; 199(4): 567 - 579. [Abstract] [Full Text] [PDF]
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G. T. Belz, C. M. Smith, D. Eichner, K. Shortman, G. Karupiah, F. R. Carbone, and W. R. Heath Cutting Edge: Conventional CD8{alpha}+ Dendritic Cells Are Generally Involved in Priming CTL Immunity to Viruses J. Immunol., February 15, 2004; 172(4): 1996 - 2000. [Abstract] [Full Text] [PDF]
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 Y. Zhang, H. Yoneyama, Y. Wang, S. Ishikawa, S.-i. Hashimoto, J.-L. Gao, P. Murphy, and K. Matsushima Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1{alpha} in Mice J Natl Cancer Inst, February 4, 2004; 96(3): 201 - 209. [Abstract] [Full Text] [PDF]
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P. Hamrah, S. O. Huq, Y. Liu, Q. Zhang, and M. R. Dana Corneal immunity is mediated by heterogeneous population of antigen-presenting cells J. Leukoc. Biol., August 1, 2003; 74(2): 172 - 178. [Abstract] [Full Text] [PDF]
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C. M. Smith, G. T. Belz, N. S. Wilson, J. A. Villadangos, K. Shortman, F. R. Carbone, and W. R. Heath Cutting Edge: Conventional CD8{alpha}+ Dendritic Cells Are Preferentially Involved in CTL Priming After Footpad Infection with Herpes Simplex Virus-1 J. Immunol., May 1, 2003; 170(9): 4437 - 4440. [Abstract] [Full Text] [PDF]
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Top
Abstract
Introduction
enhances CD40 ligand-mediated cytokine secretion by human dendritic cells (DC): a mechanism for T cell-independent DC activation.
J Immunol.
2002;168:713-722