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*
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, and
Ear, Nose and Throat Department, University of Oslo, Rikshospitalet, Oslo, Norway; and
Becton Dickinson Immunocytometry Systems, San Jose, CA 95131
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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-chain), together with
CD45RA. Our results showed that P-DCs were present in low and variable
numbers in normal nasal mucosa but increased dramatically during the
allergic reaction. This accumulation concurred with the expression of
the L-selectin ligand peripheral lymph node addressin on the mucosal
vascular endothelium. The latter observation was particularly
interesting in view of the high levels of L-selectin on circulating
P-DC precursors and of previous reports suggesting that these cells can
enter organized lymphoid tissue via high endothelial venules (which
express peripheral lymph node addressin constitutively). Together, our
findings suggested that P-DCs are involved in the triggering of airway
allergy and that they are directed to allergic lesions by adhesion
molecules that normally mediate leukocyte extravasation in organized
lymphoid tissue. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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in the presence of
certain viruses (11). Two other reports have confirmed
that plasmacytoid monocytes, natural IFN-producing cells, and immature
DCs in peripheral blood and tonsils are the same cell type (12, 13). Therefore, this distinct leukocyte subset, termed
plasmacytoid DC (P-DC), most likely has an important role both in
innate defense against pathogens and as APCs in the adaptive immune
system.
Despite such functional data obtained with isolated P-DCs, little is
known about the properties of this cell type in vivo. P-DCs have been
identified in bone marrow, blood, and organized lymphoid tissue, but
not at effector sites with direct Ag exposure, such as the skin and
mucosae. Therefore, in the present study, we examined the possible
occurrence of P-DCs in human nasal mucosa, particularly during
experimentally induced allergic rhinitis. This model should have
special relevance to the function of P-DCs in vivo, because when
matured in vitro, these cells can induce naive T cells to produce
allergy-promoting Th2 cytokines (14). In our experimental
model, extracts of grass or birch pollen were administered intranasally
to allergic rhinitis patients out of season as well as to nonallergic
volunteers. We found that P-DCs, identified by their high levels of
CD123 (IL-3R -chain) (10), were few in normal nasal
mucosa but increased dramatically during the allergic reaction. This
event coincided with the expression of the L-selectin ligand peripheral
lymph node addressin (PNAd) on the nasal vascular endothelium, which
was interesting because circulating P-DC precursors express high levels
of L-selectin (10, 12). Also, it has been reported that
P-DCs enter organized lymphoid tissue via high endothelial venules
(HEVs), where PNAd is constitutively expressed. Together, our results
suggested that P-DCs are involved in the triggering of airway allergy
and might be directed to allergic lesions by adhesion molecules that
normally mediate leukocyte extravasation in organized lymphoid
tissue.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Medical students (n = 120) were tested by skin prick test with a panel of 8 common aeroallergens and examined for allergic symptoms; 13 with allergy (age 22–29 years, 8 men and 5 women) and 7 without allergy (age 22–27 years, 5 men and 2 women) volunteered to participate in the study. Of the allergic subjects, 8 reacted with a strong positive skin response against grass and 5 reacted against birch; all had experienced typical nasal symptoms during the pollen season for >3 years. The nonatopic subjects had a negative skin prick test and no history of allergic symptoms. None of the subjects had a history of upper respiratory tract infection during the preceding 4 wk, nasal polyps, nasal surgery, or nasal deformities; neither had they taken any medication for at least 1 month before the study. All volunteers were nonsmokers and free of nasal symptoms before allergen challenge, which was performed outside the pollen season.
Study design
Study I. On day 0, a mucosal biopsy specimen was obtained from the lower turbinate of one nostril. Thereafter, the opposite nostril was challenged with relevant allergen, and clinical symptoms were subsequently recorded (see below). On day 1, another biopsy specimen was obtained from the lower turbinate of the challenged side. All subjects (patients and controls) sprayed the same nostril in a similar manner once daily for 7 days (see below). On day 8, both nostrils were subjected to biopsy of the lower turbinate.
Study II. One year later, the same test subjects (11 allergic subjects and 5 controls) participated in a study with a similar challenge protocol as described above. All subjects sprayed both nostrils daily for 7 days and peripheral blood samples were obtained on days 0, 2, 5, and 8. No biopsy was performed in study II. Both studies were approved by the National Ethics Committee, and informed written consent was obtained from each participating subject.
Nasal allergen challenge
A hand-driven pump spray was used to deliver a defined volume (50 µl) of relevant allergen solution (Aquagen timothy or Aquagen birch, ALK, Horsholm, Denmark) in the nostrils. On the first day of challenge in study I, the allergic patients were exposed unilaterally to increasing concentrations of allergen (10,000–100,000 SQ-U/ml) until a threshold dose that elicited typical acute rhinitis symptoms was established. This dose was applied in the same nostril daily for 7 days in study I and in both nostrils in study II (see above). The control subjects were exposed to the highest allergen concentration used for patients receiving Aquagen timothy. The severity of symptoms (nasal blockage, nasal discharge, and sneezing) was recorded daily on a 4-point scale (0–3) with a maximum score of 9. The median sum of individual symptom scores on each day of challenge was >6 in the patient group, and <1 in the controls.
Preparation of nasal biopsy specimens
Mucosal specimens were obtained from the lower edge of the inferior turbinate, 1.5–2 cm posterior to the front edge, by means of a Gerritsma forceps with a cup diameter of 2.5 mm. Local anesthesia was induced by placing a cotton wool carrier with 7 mg/ml tetracain/0.3 mg/ml adrenalin under the inferior turbinate adjacent to the biopsy site. Tissue samples from the same nostril were taken 0.5 cm apart. All specimens were immediately placed on a thin slice of carrot for appropriate orientation and handling, embedded in OCT (Tissue-Tek, Miles Laboratories, Elkhart, IN), and snap-frozen in liquid nitrogen as detailed elsewhere (15).
Preparation of tonsillar tissue specimens
Samples of palatine tonsils were obtained from patients operated for recurrent tonsillitis; handling and freezing were performed as described above.
Preparation of blood samples
Peripheral blood was collected by vein puncture with Vacutainers containing EDTA. Whole blood was within 2 h mixed with a NH4Cl solution (16) at room temperature for 2–5 min to lyse the erythrocytes. The leukocytes were sedimented by centrifugation, washed once with PBS containing 1% FCS, and then subjected to multicolor immunofluorescence staining (see below). Differential counts were performed at the Department of Clinical Chemistry with an automated counting system (Abbott Diagnostic Division, Irving, TX).
In vitro stimulation of PBMCs
Peripheral blood from normal donors was collected as described
above. PBMCs were separated by Lymphoprep (Nycomed Pharma, Oslo,
Norway), washed twice in PBS, and resuspended at a concentration of
1 x 106 cells/ml in RPMI-10% FCS. The
cells were then incubated overnight with or without 1000 IU/ml
recombinant human IFN--2b (Introna, Schering-Plough, Madison, NJ).
The cells were then washed twice in PBS, and cytospins (100 µl) were
prepared (1 x 106 cells/ml). These
preparations were air-dried overnight and acetone-fixed for 10 min at
room temperature.
Multicolor immunofluorescence staining
To determine tissue density, phenotype, and proliferation of
CD123high cells and the expression of PNAd by
mucosal vessel walls in situ, we applied a multicolor immunostaining
technique to acetone-fixed serial cryosections (4 µm) as described
elsewhere (15). Briefly, a mouse mAb of the IgG2a subclass
specific for human CD123 (clone 7G3, 2 µg/ml; PharMingen, San Diego,
CA) was combined with mouse mAb to either: CD4 (clone SK3 + SK4, IgG1,
10 µg/ml; Becton Dickinson Immunocytometry Systems (BDIS), San Jose,
CA); CD11c (clone KB90, IgG1, 1/10; gift from Dr. K. Pulford, Oxford,
U.K.); CD45RA (clone L48, IgG1, 1/10; BDIS); CD68 (clone KP1, IgG1,
1/500, Dako, Glostrup, Denmark); Fc
RI (clone 15-1, IgG1, 1/500; gift
from Dr. J. P. Kinet, Bethesda, MD); or HLA-DR (clone HL39, IgG3,
1/100; Sanbio, Uden, The Netherlands). In some experiments, we also
combined a mAb of the IgG1 subclass specific for human CD123 (clone
9F5, 2 µg/ml; PharMingen) with mAbs to either: CD1a (Clone NA1/34,
IgG2a, 1/10; Dako); CD14 (clone RM052, IgG2a, 3 µg/ml; Biosys,
Compeigne, France); or CD45R0 (clone UCHL-1, IgG2a, 1/10; gift from Dr.
P. C. L. Beverly, London, U.K.). All these paired mAb
mixtures were applied for 1 h at room temperature to serial
sections. Combinations of Cy3-labeled ("red") goat anti-mouse
IgG2a (1. 5 µg/ml) and biotinylated subclass-specific goat
anti-mouse IgG1 (10 µg/ml) or IgG3 (10 µg/ml) (all from
Southern Biotechnology Associates, Birmingham, AL), mixed with rabbit
antiserum to human cytokeratin (1/100; authors’ laboratory), were next
applied for 1.5 h and followed by
7-amino-4-methylcoumarin-3-acetic acid (AMCA)-labeled ("blue") goat
anti-rabbit IgG (7.5 µg/ml; Vector Laboratories, Burlingame, CA)
mixed with "green" Cy2-streptavidin (1 µg/ml; Amersham,
Galesbury, U.K.) for 30 min. The blue cytokeratin staining was included
for delineation of epithelial elements (17).
Immunostaining of T cells was performed as detailed elsewhere
(15).
To examine cell proliferation in situ, we performed immunostaining for the nuclear proliferation marker Ki-67 Ag. A mixture of mAb to CD123 (IgG2a) and mAb Ki-67 (IgG1, 1/50; DAKO) was incubated on cryosections for 1 h, followed by incubation with FITC-labeled goat anti-mouse IgG2a (10 µg/ml) and Cy3-labeled goat anti-mouse IgG1 (2 µg/ml; both from Southern Biotechnology Associates).
In situ IFN- production was evaluated by immunostaining for MxA,
which is an IFN--inducible intracellular protein well established as
a "surrogate" marker for local IFN- production
(18, 19, 20, 21). Acetone-fixed serial cryosections were immersed
in 4% paraformaldehyde for 5 min at 4°C to reduce protein leaching
during immunohistochemistry. After a brief rinse, the sections were
incubated with a combination of mouse mAb to MxA (clone M143, IgG2a,
1.5 µg/ml; courtesy Dr. O. Haller, Freiburg, Germany) and rabbit
antiserum to human cytokeratin overnight at room temperature, followed
by Cy3-labeled goat anti-mouse IgG (0.8 µg/ml, Jackson
ImmunoResearch Laboratories, West Grove, PA) and AMCA-labeled goat
anti-rabbit IgG. Adjacent sections were costained for CD123 and
CD45RA (see above) to reveal a possible correlation between the density
of MxA-expressing cells and P-DCs in nasal mucosa. As a positive
control for MxA expression, cytospins of IFN--stimulated PBMCs (see
above) were fixed and immunostained as described above. For
photographic documentation, paraformaldehyde-fixed tissue sections and
cytospins were incubated with a combination of anti-MxA (IgG2a) and
anti-CD123 (IgG1) followed by Cy3-labeled goat anti-mouse IgG2a
and FITC-labeled goat anti-mouse IgG1.
Paired fluorescence determination of the proportion and staining intensity of mucosal vessels expressing PNAd was performed with rat mAb MECA-79 applied for 1 h (IgM, 1/30; courtesy of Dr. E. C. Butcher, Stanford, CA) followed by Cy-3-conjugated ("red") goat anti-rat IgM (2 µg/ml, Jackson ImmunoResearch Laboratories) mixed with FITC-labeled ("green") Ulex europaeus lectin-1 (2 µg/ml; Vector Laboratories) for 30 min. By this approach, all vessels were decorated green, and those reactive with MECA-79 showed a mixed (yellow) color.
In all staining experiments, negative controls were obtained both by omission of primary mAbs and by incubation with irrelevant isotype- and concentration-matched primary mAbs.
Immunofluorescence microscopy of P-DCs and MECA-79-reactive vessels
The immunostained tissue sections were blindly examined by the same investigator (F.L.J.) at x400 magnification in a fluorescence microscope (Model E800, Nikon, Tokyo, Japan). To determine relevant cell density, all immunostained stromal cells (positive for one or both of the individual markers) were counted to a mucosal depth of 242 µm by superimposing a grid (242 x 242 µm) parallel to the basement membrane of the surface epithelium. At least two sections from each specimen were examined with a combination of mAbs to CD123 and CD45RA (usually a total area of more than 1 mm2) to determine the tissue density of P-DCs. Selected specimens were examined with the other marker combinations.
To evaluate endothelial MECA-79 reactivity, a scoring system was
established to combine the extent and staining intensity of
immunoreactive vessels. The vessels were divided into two groups
according to their smallest outer diameter (<15 µm or 
15 µm,
respectively) outlined by U. europaeus lectin-1 staining.
All detectable vessels, to a stromal depth of 484 µm, were counted
and graded with regard to the staining intensity for MECA-79 on an
arbitrary scale from nil (-) to strong (++). For the percentage of
MECA-79-reactive vessels, the following scores were assigned: 0, no
positive vessels; 1, 1–9% positive vessels; 2, 10–24% positive
vessels; 3, 25–40% positive vessels; and 4, >40% positive vessels.
The score for staining intensity was related to the percentage of
U. europaeus lectin-1-positive vessels deemed to react
strongly (++) with MECA-79: 1, < 2% vessels; 2, 2–20% vessels; and
3, >20% vessels. The product of these two values for numbers and
intensity of immunoreactive vessels was then used as the finally
assigned score for each specimen, which thus could have a possible
range from 0 to 12. More than 100 vessels with a diameter of <15 µm,
and 50 with a diameter of 15 µm, were counted in every
specimen.
Flow cytometric analysis
P-DC precursors in peripheral blood were identified by multicolor immunofluorescence as previously described (10). After lysis of RBC, leukocytes were labeled with PE-conjugated anti-CD123, peridinin chlorophyll protein-conjugated anti-HLA-DR, and a mixture of FITC-conjugated Abs to lineage markers that are weakly expressed on CD123high cells (CD3, CD14, CD16, CD20, CD56). These reagents (part of a kit designed to identify circulating DCs) were applied as recommended by the manufacturer (BDIS). Ab-tagged cells were examined in a FACScalibur flow cytometer (BDIS), and the data obtained were blindly analyzed with Paint-a-Gate software (BDIS). The size of the CD123high cell population was determined as the percentage of PBMCs identified by light scatter parameters.
Statistics
A Wilcoxon matched pairs sign rank sum test was performed to compare the two test groups with regard to the number of immunostained cells and the score for MECA-79-reactive vessels in nasal mucosa, as well as the number of leukocyte subsets in peripheral blood at various time points.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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To verify our ability to identify reliably P-DCs in situ, we
applied various combinations of mAbs to tonsillar cryosections. As
previously reported (10), a population of
CD123high cells was specifically decorated in the
T cell areas. Paired immunofluorescence staining showed that virtually
all of these cells distinctly coexpressed CD4, CD45RA, CD68, and HLA-DR
(Fig. 1
, a–d). Thus, the
decorated cells had the same phenotype as previously described for
plasmacytoid monocytes (2, 9) or immature
CD123high DCs (10) in tonsils. Also,
as previously reported for extravasated plasmacytoid monocytes
(9, 12), the identified P-DCs were found in close
proximity to HEVs (Fig. 1, a and b).
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Variable numbers of
CD123highCD45RA+ cells were
identified in the lamina propria of most samples of histologically
normal nasal mucosa from unchallenged allergic as well as nonallergic
individuals (Fig. 2). Interestingly,
occasional allergic patients had quite high numbers of these cells
(Fig. 2). Conversely, the epithelium always contained only few cells of
this phenotype in both test groups (median, 1 cell/mm basement
membrane; range, 0–5).
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To investigate how the
CD123highCD45RA+ P-DCs
respond to allergen, we used an established human experimental model
for atopic hypersensitivity (22). On day 1 after topical
challenge, the density of these cells was unchanged in both test groups
(Fig. 2
). However, after daily provocations for an additional 6 days,
their density increased significantly in the lamina propria of the
allergic subjects, whereas it remained unchanged in the controls (Fig. 2). Large individual variations were observed, some allergic subjects
exhibiting a very striking increase in the number of P-DCs. Parallel
histological examination by hematoxylin and eosin staining revealed
accumulation of additional mononuclear cells and eosinophils in
challenged nasal mucosa. Further staining experiments showed that most
of the former were CD4+ T cells of the memory
(CD45R0+) phenotype (data not shown).
Interestingly, however, when we immunostained for the
CD123highCD45RA+ P-DCs, the
density of such double-positive cells coincided with abundant
accumulation of mononuclear cells positive only for CD45RA (Fig. 1f). The latter turned out to be naive
(CD3+CD45RA+) T cells (data
not shown), a phenotype that hardly occurs in normal nasal mucosa
(15).
To ensure that the recruited
CD123highCD45RA+ cells
indeed were P-DCs, we performed additional immunostaining experiments
that enabled us to show that >98% of them coexpressed CD4, CD68, and
HLA-DR as described above for the tonsillar counterparts (Fig. 1, e–h). Moreover, they did not express markers such as CD11c,
CD14, CD20, and FcRI, thus confirming that they were distinct from
other types of immature DCs, monocytes, B cells, and basophils
(data not shown). Although P-DCs were present intraepithelially in
relatively small numbers, even after 7 days of allergen challenge, such
challenge resulted in a significant increase (p
= 0.003) of this subset intraepithelially in the allergic test group
(median, 8; range, 1–15) compared with the situation on day 1 (median,
0; range, 0–7).
P-DCs are distinct from CD1a+ cells in nasal mucosa
A previous study (22) based on a similar experimental
model for allergic rhinitis showed that CD1a+ DCs
accumulated in the lesion after allergen challenge with kinetics
similar to that shown here for the P-DCs. However, paired
immunostaining revealed that the CD123high DC
subset always was negative for CD1a (Fig. 3a). Interestingly, the
CD1a+ cells and the
CD123high cells were distributed differently in
nasal mucosa; the former subset predominantly occurred in the surface
epithelium as previously reported (22), whereas P-DCs were
mainly located in the lamina propria. Our finding suggested that these
two phenotypically distinct DC subsets accumulate within different
tissue compartments of allergic airway mucosa in response to allergen
challenge, which might reflect possible functional differences.
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The observed accumulation of P-DCs in allergen-challenged nasal
mucosa could be due either to increased precursor release from the bone
marrow, increased extravasation, or local proliferation. To examine the
latter possibility, we determined cellular expression of the nuclear
proliferation marker Ki-67 Ag. This marker was strongly expressed in
some epithelial cells and scattered cells in lamina propria, but no
CD123high cells were deemed to be positive (Fig. 3b). Their counterparts in tonsils were also negative for
Ki-67 Ag, as previously shown (8). Therefore, it is
unlikely that accumulation of P-DCs at either tissue site was caused by
local proliferation.
No increase of circulating P-DC precursors in allergic subjects during allergen challenge
Recent information suggests active participation of the bone marrow and the hematopoietic processes in response to allergen challenge of the airways, resulting in increased numbers of circulating inflammatory cells such as eosinophils (23). Proliferative precursors of P-DCs are found in the bone marrow (10). Therefore, we investigated whether an increase of circulating CD123high precursors could be detected in our experimental allergy model. In allergic patients, the number of eosinophils was significantly higher (p = 0.002) at all time points during the provocation compared with day 0, whereas it remained unchanged in controls. By contrast, no significant increase was observed in the number of circulating CD123high precursors during the challenge period. Before challenge, CD123high cells constituted on average 0.40 ± 0.17 and 0.47 ± 0.22% of the total number of circulating PBMCs in allergic patients and control subjects, respectively, and remained lower than 0.5% in both groups throughout the experiment (without any change in the absolute number of PBMCs). Thus, the frequency of P-DC precursors in peripheral blood agreed with those of previous reports (10, 24), and our finding suggested that the accumulation of this immature DC subset in allergen-challenged nasal mucosa primarily depended on local mechanisms.
Increased endothelial PNAd expression in allergen-challenged nasal mucosa of allergic patients
Little is known about the mechanisms directing the emigration of circulating DC precursors to various tissue sites. However, accumulation of the immature CD123high DC subset in and around HEVs in lymphoid organs (and especially in inflamed lymph nodes), suggests that P-DCs extravasate through the specialized high endothelium (9, 12). In support of this hypothesis, circulating P-DC precursors express high levels of L-selectin (10, 12), an adhesion molecule that together with PNAd form a homing receptor-endothelial ligand pair involved in lymphocyte trafficking via HEVs. Therefore, we examined vascular PNAd expression in nasal mucosa before and after allergen challenge by immunostaining for MECA-79 reactivity (25, 26).
The total score of MECA-79 reactivity was significantly increased in
nasal mucosa challenged for 7 days compared with biopsy specimens
obtained from the same nostril on day 1 (p =
0.0017), as well as from the control nostril (p
= 0.03), in all allergic patients. The reactivity was confined to
vessels with a diameter of 15 µm, and in some samples from
challenged tissue >40% of such vessels were strongly positive (Fig. 3c). Interestingly, most samples of nasal mucosa from
controls displayed some MECA-79-positive medium-sized vessels similar
to that shown for unchallenged allergic patients. This finding was
unexpected because MECA-79 reactivity is normally confined to HEVs in
organized lymphoid tissue (25, 26).
P-DC accumulation and MxA expression are unrelated in allergen-challenged nasal mucosa
Recent studies have shown that circulating P-DC precursors
correspond to the so-called natural IFN-producing cells which produce
high levels of IFN- in response to viruses and bacteria (12, 13). Therefore, we wanted to examine whether these cells reacted
in a similar manner when occurring in the allergic lesion. MxA is an
IFN--inducible protein (18, 19, 20, 21), and we used the
expression of this intracellular molecule as a surrogate marker for
IFN- production in situ. Immunostaining for MxA was performed on
paraformaldehyde-fixed sections of tonsils (n = 3) and
nasal biopsy specimens obtained on days 0 and 7 (challenged nostril)
from allergic (n = 4) and nonallergic
(n = 3) subjects. Parallel sections from both groups
showed representative densities of P-DCs. Only tonsillar tissue
sections and nasal mucosa from one allergic patient (on both day 0 and
day 7) were deemed to be weakly positive for MxA, whereas the other
nasal specimens were negative for this marker (Fig. 3d, and
data not shown). IFN--stimulated PBMCs served as a strong positive
control for MxA expression (Fig. 3e), whereas unstimulated
PBMCs were negative (Fig. 3f). This finding suggested that
P-DCs did not produce substantial amounts of IFN- in
allergen-challenged nasal mucosa of allergic patients.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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in
response to viruses and bacteria (13, 27), whereas they,
after differentiation to DCs in vitro, effectively can stimulate naive
T cells to produce immunoregulatory cytokines (14, 27, 28). However, little is known about the function of P-DCs in
vivo. Contrary to other DC types, P-DCs have previously been identified
only in bone marrow, peripheral blood, and organized lymphoid tissue
but not at epithelial surfaces where immature DCs are presumed to be
involved in surveillance against microbial Ags (29). It
was therefore of considerable interest that these cells accumulated
abundantly in nasal mucosa of experimentally challenged allergic
rhinitis patients. This finding clearly demonstrated that P-DCs can
migrate to a site of inflammation outside organized lymphoid
tissue.
Our results suggested that P-DCs are involved in the pathogenesis of
nasal allergy. As differentiated P-DCs, these cells appear to have an
inherent capacity to induce naive T cells to produce allergy-promoting
Th2 cytokines (14), which are believed to play a key role
in allergic rhinitis (30). Alternatively, the P-DCs can
produce large amounts of IFN- (11, 12, 13), a cytokine
associated with Th1-type immunity (31). Production of
IFN- could thus play a role in counteracting a Th2-polarized
allergic microenvironment. Therefore, we examined whether P-DCs in the
allergic lesion had produced IFN- in situ. MxA is an
IFN--inducible cytoplasmic protein that mediates resistance to
viruses, and its detection is frequently used as a surrogate marker for
local IFN- production (19, 20). However, only low and
inconsistent levels of nasal MxA expression were detected. Thus, it is
unlikely that P-DCs produced IFN- locally to limit the allergic
reaction.
Although little is known about the in vivo properties of P-DCs, recent
in vitro data strongly suggest that these cells may participate in
various types of inflammatory disorders besides allergy. Indeed, we
have recently identified P-DCs in certain chronic inflammatory skin
diseases known to be associated with local MxA expression, such as
lupus erythematosus and lichen planus (L. Farkas, K. Beiske, F.
Lund-Johansen, P. Brandtzaeg, and F. L. Jahnsen, manuscript in
preparation), suggesting that they also can produce IFN- in vivo.
Interestingly, however, P-DCs were virtually absent from various
nonallergic chronic inflammatory disorders occurring in nasal or
intestinal mucosa, such as nasal polyps, celiac disease, and
inflammatory bowel disease (F. L. Jahnsen, L. Farkas, H. S. Carlsen,
and P. Brandtzaeg, unpublished observations). Thus, tissue accumulation
of P-DCs appears to be restricted to certain lesions and is neither an
exclusive nor a common feature of mucosal inflammation. To gain further
knowledge about the possible role of P-DCs in human pathology, we are
currently examining the distribution of this cell type and the local
expression of MxA in a variety of inflammatory lesions.
HEVs express L-selectin ligands (also called PNAd, identifiable by mAb MECA-79) that mediate L-selectin-dependent rolling of naive lymphocytes. Circulating P-DC precursors express high levels of L-selectin (10, 12), which most likely explains their extravasation preference in HEV-containing organized lymphoid tissue. Interestingly, therefore, we found that challenged allergic nasal mucosa, in which P-DCs accumulated abundantly, contained many medium-sized strongly MECA-79-reactive blood vessels. This finding was intriguing because MECA-79 reactivity is normally restricted to organized lymphoid tissue (26). A role for PNAd in leukocyte recruitment to the allergic nasal lesion was further supported by the finding that CD45RA+ T cells were abundantly present in the same allergen-challenged biopsy specimens (data not shown). Leukocyte extravasation is a multistep process, involving several adhesion molecules and chemoattractants (32). Previous studies have shown that endothelial expression of both ICAM-1 and VCAM-1 are increased in a similar human model for allergic rhinitis (33, 34). P-DC precursors express ligands for both endothelial receptors (10, 12), suggesting that they, together with PNAd, could be involved in the extravasation of P-DCs in nasal allergy. The likely additional requirements for selected chemokines is currently under investigation in our laboratory. Endothelial PNAd expression has likewise been demonstrated in various chronic inflammatory skin disorders (26, 35), which supports the notion that this addressin is involved in leukocyte recruitment to sites of inflammation. To further elucidate this possibility, we are currently examining whether accumulation of P-DCs in certain inflammatory skin lesions, as discussed above, might be related to local endothelial MECA-79 reactivity.
We also tested the possibility that increased precursor release from the bone marrow, or local proliferation, could have contributed to the increased number of P-DCs in nasal mucosa after allergen challenge. A significant elevation of circulating eosinophils suggested that the bone marrow was stimulated by this challenge, but the number of circulating P-DC precursors remained unaltered (0.4–0.5% of all PBMCs) at a level similar to that previously reported (10, 24, 36). This observation, together with the fact that the nasal P-DCs did not express the proliferation marker Ki-67 Ag, suggested that neither precursor release from the bone marrow nor local proliferation contributed significantly to their accumulation in the allergic lesion.
In summary, P-DCs that previously have been observed only in bone marrow, peripheral blood, and organized lymphoid tissue were found to extravasate abundantly into nasal mucosa during an induced allergic reaction. Because this DC type can promote a Th2 response in vitro (14), our results suggested the interesting possibility that they contribute to airway allergy.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Per Brandtzaeg, Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, Rikshospitalet, N-0027 Oslo, Norway.
3 Abbreviations used in this paper: DC, dendritic cell; P-DC, plasmacytoid DC; PNAd, peripheral lymph node addressin; HEV, high endothelial venule; AMCA, 7-amino-4-methylcoumarin-3-acetic acid; BDIS, Becton Dickinson Immunocytometry Systems.
Received for publication January 10, 2000. Accepted for publication July 18, 2000.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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producing cells as determined by flow cytometry. Scand. J. Immunol. 44:164.[Medline]
-interferon and its induced protein, MxA, in Alzheimer’s and Parkinson’s disease brain tissues. Neurosci. Lett. 181:61.[Medline]
ß, MxA, 2',5'-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells. J. Immunol. 158:2363.[Abstract]
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 H. Donaghy, L. Bosnjak, A. N. Harman, V. Marsden, S. K. Tyring, T.-C. Meng, and A. L. Cunningham Role for Plasmacytoid Dendritic Cells in the Immune Control of Recurrent Human Herpes Simplex Virus Infection J. Virol., February 15, 2009; 83(4): 1952 - 1961. [Abstract] [Full Text] [PDF]
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 C. Albanesi, C. Scarponi, S. Pallotta, R. Daniele, D. Bosisio, S. Madonna, P. Fortugno, S. Gonzalvo-Feo, J.-D. Franssen, M. Parmentier, et al. Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment J. Exp. Med., January 16, 2009; 206(1): 249 - 258. [Abstract] [Full Text] [PDF]
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G. Gerlini, G. Mariotti, A. Chiarugi, P. Di Gennaro, R. Caporale, A. Parenti, L. Cavone, A. Tun-Kyi, F. Prignano, R. Saccardi, et al. Induction of CD83+CD14+ Nondendritic Antigen-Presenting Cells by Exposure of Monocytes to IFN-{alpha} J. Immunol., September 1, 2008; 181(5): 2999 - 3008. [Abstract] [Full Text] [PDF]
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D. W. Pascual, X. Wang, I. Kochetkova, G. Callis, and C. Riccardi The Absence of Lymphoid CD8+ Dendritic Cell Maturation in L-Selectin-/- Respiratory Compartment Attenuates Antiviral Immunity J. Immunol., July 15, 2008; 181(2): 1345 - 1356. [Abstract] [Full Text] [PDF]
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 A. Shin, T. Toy, S. Rothenfusser, N. Robson, J. Vorac, M. Dauer, M. Stuplich, S. Endres, J. Cebon, E. Maraskovsky, et al. P2Y receptor signaling regulates phenotype and IFN-{alpha} secretion of human plasmacytoid dendritic cells Blood, March 15, 2008; 111(6): 3062 - 3069. [Abstract] [Full Text] [PDF]
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 J.-W. Eijgenraam, S. M. Reinartz, S. W. A. Kamerling, V. J. van Ham, K. Zuidwijk, C. M. van Drunen, M. R. Daha, W. J. Fokkens, and C. van Kooten Immuno-histological analysis of dendritic cells in nasal biopsies of IgA nephropathy patients Nephrol. Dial. Transplant., February 1, 2008; 23(2): 612 - 620. [Abstract] [Full Text] [PDF]
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 M. Lommatzsch, K. Bratke, A. Bier, P. Julius, M. Kuepper, W. Luttmann, and J. C. Virchow Airway dendritic cell phenotypes in inflammatory diseases of the human lung Eur. Respir. J., November 1, 2007; 30(5): 878 - 886. [Abstract] [Full Text] [PDF]
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E. O. Kvale, Y. Floisand, F. Lund-Johansen, H. Rollag, L. Farkas, S. Ghanekar, P. Brandtzaeg, F. L. Jahnsen, and J. Olweus Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells Blood, April 15, 2007; 109(8): 3369 - 3376. [Abstract] [Full Text] [PDF]
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 K. Bratke, M. Lommatzsch, P. Julius, M. Kuepper, H.-D. Kleine, W. Luttmann, and J Christian Virchow Dendritic cell subsets in human bronchoalveolar lavage fluid after segmental allergen challenge Thorax, February 1, 2007; 62(2): 168 - 175. [Abstract] [Full Text] [PDF]
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H. Donaghy, J. Wilkinson, and A. L. Cunningham HIV interactions with dendritic cells: has our focus been too narrow? J. Leukoc. Biol., November 1, 2006; 80(5): 1001 - 1012. [Abstract] [Full Text] [PDF]
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 E. Hartmann, H. Graefe, A. Hopert, R. Pries, S. Rothenfusser, H. Poeck, B. Mack, S. Endres, G. Hartmann, and B. Wollenberg Analysis of Plasmacytoid and Myeloid Dendritic Cells in Nasal Epithelium Clin. Vaccine Immunol., November 1, 2006; 13(11): 1278 - 1286. [Abstract] [Full Text] [PDF]
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P. d. Nadai, A.-S. Charbonnier, C. Chenivesse, S. Senechal, C. Fournier, J. Gilet, H. Vorng, Y. Chang, P. Gosset, B. Wallaert, et al. Involvement of CCL18 in Allergic Asthma J. Immunol., May 15, 2006; 176(10): 6286 - 6293. [Abstract] [Full Text] [PDF]
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 P. Ettmayer, P. Mayer, F. Kalthoff, W. Neruda, N. Harrer, G. Hartmann, M. M. Epstein, V. Brinkmann, C. Heusser, and M. Woisetschlager A Novel Low Molecular Weight Inhibitor of Dendritic Cells and B Cells Blocks Allergic Inflammation Am. J. Respir. Crit. Care Med., March 15, 2006; 173(6): 599 - 606. [Abstract] [Full Text] [PDF]
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L. Chaperot, A. Blum, O. Manches, G. Lui, J. Angel, J.-P. Molens, and J. Plumas Virus or TLR Agonists Induce TRAIL-Mediated Cytotoxic Activity of Plasmacytoid Dendritic Cells J. Immunol., January 1, 2006; 176(1): 248 - 255. [Abstract] [Full Text] [PDF]
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J. T. Schroeder, A. P. Bieneman, H. Xiao, K. L. Chichester, K. Vasagar, S. Saini, and M. C. Liu TLR9- and Fc{epsilon}RI-Mediated Responses Oppose One Another in Plasmacytoid Dendritic Cells by Down-Regulating Receptor Expression J. Immunol., November 1, 2005; 175(9): 5724 - 5731. [Abstract] [Full Text] [PDF]
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A. Smed-Sorensen, K. Lore, J. Vasudevan, M. K. Louder, J. Andersson, J. R. Mascola, A.-L. Spetz, and R. A. Koup Differential Susceptibility to Human Immunodeficiency Virus Type 1 Infection of Myeloid and Plasmacytoid Dendritic Cells J. Virol., July 15, 2005; 79(14): 8861 - 8869. [Abstract] [Full Text] [PDF]
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R. Morita, T. Uchiyama, and T. Hori Nitric Oxide Inhibits IFN-{alpha} Production of Human Plasmacytoid Dendritic Cells Partly via a Guanosine 3',5'-Cyclic Monophosphate-Dependent Pathway J. Immunol., July 15, 2005; 175(2): 806 - 812. [Abstract] [Full Text] [PDF]
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F.-E. Johansen, E. S. Baekkevold, H. S. Carlsen, I. N. Farstad, D. Soler, and P. Brandtzaeg Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: dispersion from tonsils Blood, July 15, 2005; 106(2): 593 - 600. [Abstract] [Full Text] [PDF]
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F. O. Nestle, C. Conrad, A. Tun-Kyi, B. Homey, M. Gombert, O. Boyman, G. Burg, Y.-J. Liu, and M. Gilliet Plasmacytoid predendritic cells initiate psoriasis through interferon-{alpha} production J. Exp. Med., July 5, 2005; 202(1): 135 - 143. [Abstract] [Full Text] [PDF]
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J. N. Samsom, L. A. van Berkel, J. M. L. M. van Helvoort, W. W. J. Unger, W. Jansen, T. Thepen, R. E. Mebius, S. S. Verbeek, and G. Kraal Fc{gamma}RIIB Regulates Nasal and Oral Tolerance: A Role for Dendritic Cells J. Immunol., May 1, 2005; 174(9): 5279 - 5287. [Abstract] [Full Text] [PDF]
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 A. J. Thorley, P. Goldstraw, A. Young, and T. D. Tetley Primary Human Alveolar Type II Epithelial Cell CCL20 (Macrophage Inflammatory Protein-3{alpha})-Induced Dendritic Cell Migration Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 262 - 267. [Abstract] [Full Text] [PDF]
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I. B. Bekeredjian-Ding, M. Wagner, V. Hornung, T. Giese, M. Schnurr, S. Endres, and G. Hartmann Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN J. Immunol., April 1, 2005; 174(7): 4043 - 4050. [Abstract] [Full Text] [PDF]
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S. Vuckovic, D. Khalil, N. Angel, F. Jahnsen, I. Hamilton, A. Boyce, B. Hock, and D. N. J. Hart The CMRF58 antibody recognizes a subset of CD123hi dendritic cells in allergen-challenged mucosa J. Leukoc. Biol., March 1, 2005; 77(3): 344 - 351. [Abstract] [Full Text] [PDF]
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H. Hashizume, T. Horibe, H. Yagi, N. Seo, and M. Takigawa Compartmental Imbalance and Aberrant Immune Function of Blood CD123+ (Plasmacytoid) and CD11c+ (Myeloid) Dendritic Cells in Atopic Dermatitis J. Immunol., February 15, 2005; 174(4): 2396 - 2403. [Abstract] [Full Text] [PDF]
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 J. A. Woodfolk Allergy and Dermatophytes Clin. Microbiol. Rev., January 1, 2005; 18(1): 30 - 43. [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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B. A. Zabel, A. M. Silverio, and E. C. Butcher Chemokine-Like Receptor 1 Expression and Chemerin-Directed Chemotaxis Distinguish Plasmacytoid from Myeloid Dendritic Cells in Human Blood J. Immunol., January 1, 2005; 174(1): 244 - 251. [Abstract] [Full Text] [PDF]
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N. Kohrgruber, M. Groger, P. Meraner, E. Kriehuber, P. Petzelbauer, S. Brandt, G. Stingl, A. Rot, and D. Maurer Plasmacytoid Dendritic Cell Recruitment by Immobilized CXCR3 Ligands J. Immunol., December 1, 2004; 173(11): 6592 - 6602. [Abstract] [Full Text] [PDF]
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R. Lande, E. Giacomini, B. Serafini, B. Rosicarelli, G. D. Sebastiani, G. Minisola, U. Tarantino, V. Riccieri, G. Valesini, and E. M. Coccia Characterization and Recruitment of Plasmacytoid Dendritic Cells in Synovial Fluid and Tissue of Patients with Chronic Inflammatory Arthritis J. Immunol., August 15, 2004; 173(4): 2815 - 2824. [Abstract] [Full Text] [PDF]
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J.-F. Fonteneau, M. Larsson, A.-S. Beignon, K. McKenna, I. Dasilva, A. Amara, Y.-J. Liu, J. D. Lifson, D. R. Littman, and N. Bhardwaj Human Immunodeficiency Virus Type 1 Activates Plasmacytoid Dendritic Cells and Concomitantly Induces the Bystander Maturation of Myeloid Dendritic Cells J. Virol., May 15, 2004; 78(10): 5223 - 5232. [Abstract] [Full Text] [PDF]
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S. Pichyangkul, K. Yongvanitchit, U. Kum-arb, H. Hemmi, S. Akira, A. M. Krieg, D. G. Heppner, V. A. Stewart, H. Hasegawa, S. Looareesuwan, et al. Malaria Blood Stage Parasites Activate Human Plasmacytoid Dendritic Cells and Murine Dendritic Cells through a Toll-Like Receptor 9-Dependent Pathway J. Immunol., April 15, 2004; 172(8): 4926 - 4933. [Abstract] [Full Text] [PDF]
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T. Ito, R. Amakawa, M. Inaba, T. Hori, M. Ota, K. Nakamura, M. Takebayashi, M. Miyaji, T. Yoshimura, K. Inaba, et al. Plasmacytoid Dendritic Cells Regulate Th Cell Responses through OX40 Ligand and Type I IFNs J. Immunol., April 1, 2004; 172(7): 4253 - 4259. [Abstract] [Full Text] [PDF]
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N. J. Megjugorac, H. A. Young, S. B. Amrute, S. L. Olshalsky, and P. Fitzgerald-Bocarsly Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells J. Leukoc. Biol., March 1, 2004; 75(3): 504 - 514. [Abstract] [Full Text] [PDF]
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M. Schnurr, T. Toy, A. Shin, G. Hartmann, S. Rothenfusser, J. Soellner, I. D. Davis, J. Cebon, and E. Maraskovsky Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells Blood, February 15, 2004; 103(4): 1391 - 1397. [Abstract] [Full Text] [PDF]
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F. L. Jahnsen, E. Gran, R. Haye, and P. Brandtzaeg Human Nasal Mucosa Contains Antigen-Presenting Cells of Strikingly Different Functional Phenotypes Am. J. Respir. Cell Mol. Biol., January 1, 2004; 30(1): 31 - 37. [Abstract] [Full Text] [PDF]
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C. Asselin-Paturel, G. Brizard, J.-J. Pin, F. Briere, and G. Trinchieri Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody J. Immunol., December 15, 2003; 171(12): 6466 - 6477. [Abstract] [Full Text] [PDF]
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A. K. Palucka, J. Gatlin, J. P. Blanck, M. W. Melkus, S. Clayton, H. Ueno, E. T. Kraus, P. Cravens, L. Bennett, A. Padgett-Thomas, et al. Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors Blood, November 1, 2003; 102(9): 3302 - 3310. [Abstract] [Full Text] [PDF]
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 E. Hartmann, B. Wollenberg, S. Rothenfusser, M. Wagner, D. Wellisch, B. Mack, T. Giese, O. Gires, S. Endres, and G. Hartmann Identification and Functional Analysis of Tumor-Infiltrating Plasmacytoid Dendritic Cells in Head and Neck Cancer Cancer Res., October 1, 2003; 63(19): 6478 - 6487. [Abstract] [Full Text] [PDF]
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B. Vanbervliet, N. Bendriss-Vermare, C. Massacrier, B. Homey, O. de Bouteiller, F. Briere, G. Trinchieri, and C. Caux The Inducible CXCR3 Ligands Control Plasmacytoid Dendritic Cell Responsiveness to the Constitutive Chemokine Stromal Cell-derived Factor 1 (SDF-1)/CXCL12 J. Exp. Med., September 2, 2003; 198(5): 823 - 830. [Abstract] [Full Text] [PDF]
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 E. S. Baekkevold, M. Roussigne, T. Yamanaka, F.-E. Johansen, F. L. Jahnsen, F. Amalric, P. Brandtzaeg, M. Erard, G. Haraldsen, and J.-P. Girard Molecular Characterization of NF-HEV, a Nuclear Factor Preferentially Expressed in Human High Endothelial Venules Am. J. Pathol., July 1, 2003; 163(1): 69 - 79. [Abstract] [Full Text] [PDF]
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G. de la Rosa, N. Longo, J. L. Rodriguez-Fernandez, A. Puig-Kroger, A. Pineda, A. L. Corbi, and P. Sanchez-Mateos Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration J. Leukoc. Biol., May 1, 2003; 73(5): 639 - 649. [Abstract] [Full Text] [PDF]
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J.-F. Fonteneau, M. Gilliet, M. Larsson, I. Dasilva, C. Munz, Y.-J. Liu, and N. Bhardwaj Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity Blood, May 1, 2003; 101(9): 3520 - 3526. [Abstract] [Full Text] [PDF]
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A. Mazzoni, C. A. Leifer, G. E. D. Mullen, M. N. Kennedy, D. M. Klinman, and D. M. Segal Cutting Edge: Histamine Inhibits IFN-{alpha} Release from Plasmacytoid Dendritic Cells J. Immunol., March 1, 2003; 170(5): 2269 - 2273. [Abstract] [Full Text] [PDF]
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A.-S. Charbonnier, H. Hammad, P. Gosset, G. A. Stewart, S. Alkan, A.-B. Tonnel, and J. Pestel Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response J. Leukoc. Biol., January 1, 2003; 73(1): 91 - 99. [Abstract] [Full Text] [PDF]
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P. Brawand, D. R. Fitzpatrick, B. W. Greenfield, K. Brasel, C. R. Maliszewski, and T. De Smedt Murine Plasmacytoid Pre-Dendritic Cells Generated from Flt3 Ligand-Supplemented Bone Marrow Cultures Are Immature APCs J. Immunol., December 15, 2002; 169(12): 6711 - 6719. [Abstract] [Full Text] [PDF]
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H. Matsuda, T. Suda, H. Hashizume, K. Yokomura, K. Asada, K. Suzuki, K. Chida, and H. Nakamura Alteration of Balance between Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in Peripheral Blood of Patients with Asthma Am. J. Respir. Crit. Care Med., October 15, 2002; 166(8): 1050 - 1054. [Abstract] [Full Text] [PDF]
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L. Fong, M. Mengozzi, N. W. Abbey, B. G. Herndier, and E. G. Engleman Productive Infection of Plasmacytoid Dendritic Cells with Human Immunodeficiency Virus Type 1 Is Triggered by CD40 Ligation J. Virol., October 2, 2002; 76(21): 11033 - 11041. [Abstract] [Full Text] [PDF]
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J. H. Ahn, Y. Lee, C. Jeon, S.-J. Lee, B.-H. Lee, K. D. Choi, and Y.-S. Bae Identification of the genes differentially expressed in human dendritic cell subsets by cDNA subtraction and microarray analysis Blood, August 13, 2002; 100(5): 1742 - 1754. [Abstract] [Full Text] [PDF]
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E. J. Soilleux, L. S. Morris, G. Leslie, J. Chehimi, Q. Luo, E. Levroney, J. Trowsdale, L. J. Montaner, R. W. Doms, D. Weissman, et al. Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro J. Leukoc. Biol., March 1, 2002; 71(3): 445 - 457. [Abstract] [Full Text] [PDF]
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A. Dzionek, Y. Sohma, J. Nagafune, M. Cella, M. Colonna, F. Facchetti, G. Gunther, I. Johnston, A. Lanzavecchia, T. Nagasaka, et al. BDCA-2, a Novel Plasmacytoid Dendritic Cell-specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon {alpha}/{beta} Induction J. Exp. Med., December 17, 2001; 194(12): 1823 - 1834. [Abstract] [Full Text] [PDF]
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F L Jahnsen, E D Moloney, T Hogan, J W Upham, C M Burke, and P G Holt Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge Thorax, November 1, 2001; 56(11): 823 - 826. [Abstract] [Full Text] [PDF]
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H. Nakano, M. Yanagita, and M. D. Gunn Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells J. Exp. Med., October 15, 2001; 194(8): 1171 - 1178. [Abstract] [Full Text] [PDF]
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G. Penna, S. Sozzani, and L. Adorini Cutting Edge: Selective Usage of Chemokine Receptors by Plasmacytoid Dendritic Cells J. Immunol., August 15, 2001; 167(4): 1862 - 1866. [Abstract] [Full Text] [PDF]
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 S Blomberg, M L Eloranta, B Cederblad, K Nordlind, G L Alm, and L Ronnblom Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus Lupus, July 1, 2001; 10(7): 484 - 490. [Abstract] [PDF]
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L. Farkas, K. Beiske, F. Lund-Johansen, P. Brandtzaeg, and F. L. Jahnsen Plasmacytoid Dendritic Cells (Natural Interferon- {{alpha}}/{beta}-Producing Cells) Accumulate in Cutaneous Lupus Erythematosus Lesions Am. J. Pathol., July 1, 2001; 159(1): 237 - 243. [Abstract] [Full Text] [PDF]
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