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Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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and IL-12, but diminished IL-10 mRNA expression. Moreover, DCs
treated with anti-IL-10 Ab showed an increased capacity to activate
allogeneic T cells and primed naive T cells to a more prominent Th1
polarization. DC maturation and IL-10 neutralization were associated
with enhanced accumulation of the IL-10 receptor binding chain
(IL-10R1) mRNA and intracellular IL-10R1 protein. In contrast, surface
IL-10R1 and IL-10 binding activity diminished in mature DCs. These
results indicate that autocrine IL-10 prevents spontaneous maturation
of DCs in vitro, limits LPS- and CD40-mediated maturation, and
increases IL-10 production by DCs. Moreover, IL-10R expression appears
to be regulated by both transcriptional and posttranscriptional
mechanisms. Endogenous IL-10 and IL-10R can be relevant targets for the
manipulation of DC functions. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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To prevent exaggerated and unwanted immune responses, DC maturation and functions are tightly regulated. IL-10 has been identified as a major factor that can prevent the differentiation of DCs from monocytes and strongly inhibit DC maturation induced by different stimuli (9, 10, 11, 12, 13, 14). In particular, IL-10 blocks the up-regulation of costimulatory molecules and IL-12 production and thus impairs the ability of DCs to generate Th1 responses (15). IL-10-treated DCs are not only less efficient at stimulating T cell responses but can induce a state of Ag-specific tolerance (9, 16, 17). IL-10 can be secreted by different cell types, including monocytes, mast cells, T regulatory cells, and tumor cells, and has an important role in limiting allergic and autoimmune reactions or in mediating tumor escape from immune surveillance (17, 18). In contrast, several reports have shown that mature DCs are no longer sensitive to the inhibitory effects of IL-10 (14, 15, 17, 19, 20, 21), but the molecular bases of this phenomenon are as yet unknown. IL-10 exerts its actions through a heterodimeric membrane receptor formed by a binding chain (IL-10R1) and a transducing chain (IL-10R2, also known as CFR2–4), whose mutual interaction activates a series of intracellular signaling molecules, including STAT proteins (22, 23, 24, 25, 26, 27, 28, 29).
Although some DC subsets can produce IL-10 (3, 13, 30, 31, 32), the impact of endogenous IL-10 on DC biology has been only marginally investigated (13, 33). In this work, we provide evidence that autocrine IL-10 serves as a potent mechanism for limiting the maturation of monocyte-derived DCs and their capacity to initiate Th1 responses. Moreover, we show that mature DCs accumulate higher amounts of IL-10R1 mRNA and intracellular IL-10R1 protein but reduce surface IL-10R1 expression and IL-10 binding activity. Thus, endogenous IL-10 and IL-10R appear to be important regulators of DC biology and can represent relevant targets for the manipulation of DC functions.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Streptococcus gordonii strain GP1221 was a gift from
Dr. D. Medaglini (University of Siena, Siena, Italy), and
Salmonella typhi (Neotyf) was provided by Chiron Italia
(Siena, Italy). LPS (from Salmonella typhimurium),
lipoteichoic acid (LTA; from Staphylococcus
aureus), and poly I:C were purchased from
Sigma-Aldrich (Milan, Italy). Soluble CD40L (sCD40L) was obtained from
Alexis (San Diego, CA). It is composed of the extracellular domain of
human CD40L fused to the N terminus of a linker peptide and a FLAG-tag
and was used together with an enhancer that increases the biological
activity of sCD40L. The mAbs FITC-conjugated and pure anti-HLA-DR
(L243), FITC-conjugated anti-CD14 (M
P9), anti-CD3 (SK7),
anti-CD4 (SK3), and anti-CD45RA (L48) were obtained from Becton
Dickinson (San Jose, CA). FITC-conjugated anti-CD1a (HI149),
anti-CD86 (2331), anti-CD40 (5C3), anti-IFN-
(4S.B3),
pure anti-CD28 (CD28.2), PE-conjugated anti-IL-4 (MP4–25D2,
rat), and pure anti-CD45RO (UCHL1) were obtained from BD PharMingen
(San Diego, CA). FITC-conjugated anti-CD54 (84H10) and
anti-CD80 (MAB104), and pure anti-CD83 (HB15A) and anti-CD3
(UCHT1) came from Immunotech (Marseille, France). Anti-MHC class I
(W6/32) was obtained from Dako (Glostrup, Denmark). Control mouse or
rat Ig were obtained from Becton Dickinson or BD PharMingen. The mouse
mAb anti-human IL-10 (23738.11) came from R&D Systems (Minneapolis,
MN), and the rat anti-human IL-10R1 mAb 3F9 was obtained from BD
PharMingen. Anti-IL-10 mAb and sCD40L had undetectable endotoxin levels
(<10 pg/mg) by the Limulus amebocyte lysate assay
(BioWhittaker, Walkersville, MD).
DC preparation and stimulation
DCs were prepared from PBMC of healthy individuals as described previously (3). Briefly, PBMC were separated on multistep Percoll gradients (Pharmacia, Uppsala, Sweden), and cells from the light density fraction (42.5–50%; >90% CD14+) were cultured at 1 x 106 cells/ml in RPMI 1640 (Life Technologies, Gaithersburg, MD) containing 1 mM sodium pyruvate, 0.1 mM nonessential amino acids, 2 mM L-glutamine, 25 mM HEPES, 100 U/ml penicillin, 100 µg/ml streptomycin (all obtained from Life Technologies), and 0.05 mM 2-ME (Merck, Darmstadt, Germany) (complete RPMI), and supplemented with 10% FBS (HyClone, Logan, UT), 100 ng/ml human rGM-CSF (Mielogen, Schering-Plough, Milan, Italy), and 200 U/ml human rIL-4 (R&D Systems) at 37°C with 5% CO2. Medium was changed after 3 days, and at day 6 of culture, cells were recovered and depleted of CD2+ and CD19+ cells by means of immunomagnetic beads coated with specific mAbs (Dynal, Oslo, Norway). This procedure gave >97% pure CD1a+ and CD14- DC preparations. DCs were incubated in 6-well plates (1 x 106 cells/ml) at 37°C with S. gordonii (bacteria-to-DCs ratio, 50:1), S. typhi (bacteria-to-DCs ratio, 1:1), LPS (10 µg/ml), LTA (10 µg/ml), poly I:C (100 ng/ml), or sCD40L (1 µg/ml). Where indicated, DCs were treated with anti-HLA-DR mAb (10 µg/ml) for 1 h at 4°C, washed, and cultured at 37°C in the presence or absence of sCD40L. To block endogenous IL-10, the neutralizing anti-IL-10 mAb or mouse Ig were added to unstimulated DC cultures or at the time of stimulation with LPS or sCD40L, and cells were analyzed after 18 h. Preliminary dose-response experiments indicated that the optimal neutralizing dose of anti-IL-10 mAb was 10 µg/ml.
ELISA
Measurement of IL-12 (p70) and TNF- in DC supernatants was
performed by using OptEIA kits from BD PharMingen, as per the
manufacturer’s protocol. IL-10R1 was determined in DC supernatants and
cell lysates by using the Ab pair mouse mAb 370607.11 for coating and
goat polyclonal biotinylated AF-274-NA for detection (R&D Systems).
Flow cytometry analysis of DCs
DCs either untreated or stimulated for 18 h with LPS or sCD40L in the presence of anti-IL-10 mAb or control IgG were washed and then incubated in PBS containing 2% FBS and 0.01% NaN3 with FITC-conjugated mAbs for 40 min at 4°C. When pure mAbs were used, a secondincubation with a FITC-coupled goat (Fab')2 anti-mouse IgG (Southern Biotechnology Associates, Birmingham, AL) was performed. Matched isotype mouse Ig were used in control samples. Binding of biotinylated IL-10 was performed on DCs fixed with 2% paraformaldehyde by using the Fluorokine kit (R&D Systems), as per the manufacturers’ protocol. To detect intracellular IL-10R and IL-10 binding activity, DCs were fixed and permeabilized with 0.5% saponin prior the staining. Cells were analyzed in a FACScan equipped with CellQuest software (Becton Dickinson, Mountain View, CA).
DC-T cell cocultures
For the primary MLR assay, T lymphocytes were purified (>95%
CD3+) from the heavy-density fraction (50–60%)
of Percoll gradients followed by immunomagnetic depletion with a
mixture of anti-MHC class II- and anti-CD19 mAb-conjugated
beads (Dynal). DCs were washed and then cultured in 96-well
microculture plates in serial dilutions (78 to 5 x
103 cells/well) together with purified allogeneic
T lymphocytes (1.5 x 105 cells/well) in
complete RPMI supplemented with 5% human serum (Sigma). Cocultures
were pulsed at day 3 with 1 µCi/well
[3H]thymidine (Amersham, Little Chalfont, U.K.)
for 
16 h at 37°C and then harvested onto fiber-coated 96-well
plates (Packard Instruments, Groningen, The Netherlands). Radioactivity
was measured in a 
-counter (Topcount; Packard Instruments). Results
are given as mean cpm ± SD of triplicate cultures. Where
indicated, allogeneic naive T cells were purified (>95%
CD45RA+) by incubation of
CD3+ T cells with anti-CD45RO mAb followed by
a goat anti-mouse Ig coupled to immunomagnetic beads (Dynal), and
then cocultured (106 cells/well) with DCs (5
x 104 cells/well) in 24-well plates in complete
RPMI plus 5% human serum. After 6 days, T cells were restimulated with
plate-coated anti-CD3 and soluble anti-CD28 mAbs (both at 1
µg/ml) and examined for IFN- and IL-4 production. Two-color
intracellular staining for IFN- and IL-4 was performed 6 h
after stimulation. Monensin (10 µM; Sigma) and brefeldin A (10
µg/ml; Sigma) were added into the cultures before the staining to
prevent cytokine secretion. T cells then were fixed with 2%
paraformaldehyde, permeabilized with 0.5% saponin, stained with
FITC-conjugated mouse anti-IFN- and PE-conjugated rat
anti-IL-4, and finally analyzed with a FACScan. In control samples,
staining was performed by using isotype-matched control Ig. In parallel
samples, cytokines were measured in the T cell supernatants 48 h
after activation by ELISA by using matched pairs of mAbs (for IL-4 and
IFN-) and OptEIA kit (for IL-5) from BD PharMingen. T cells that
were not restimulated at day 6 did not show any lymphokine production
(data not shown).
Northern blot analysis
The probes specific for human IL-10, IL-10R1, and IL-10R2 were obtained by RT-PCR on RNA isolated from purified DCs. IL-10-specific synthetic oligonucleotides were 5'-GAA GGA TCA GCT GGA CAA CTT GTTG-3' and 5'-CTC ATG GCT TTG TAG ATG CCT TTC TC-3'.IL-10R1- and IL-10R2-specific primer pairs were 5'-CCG TCT GTG TGG TTT GAA GCA GAA-3' and 5'-GAT GAT GAC GTT GGT CAC GGT GAA-3' (22), and 5'-GAG TCA CCT GCT TTT GCC AAA GGG-3' and 5'-CAT GGG TTG TTT GCT CAC AGA CAG-3' (24), respectively. Amplificates were cloned into pCR-TOPO vector (Invitrogen, Carlsbad, CA), and then subjected to an automated sequence analysis with a Perkin-Elmer sequencer (model ABI Prism 377 XL; Perkin-Elmer, Norwalk, CT). Total RNA was extracted from DCs by using the TRIzol solution (Life Technologies), fractionated on denaturing-agarose gels, and blotted to nylon membranes (Amersham Pharmacia Biotech, Milan, Italy). After UV fixation, the membranes were hybridized with 32P-radiolabeled probes for 1 h at 68°C in Quickhyb solution (Stratagene, La Jolla, CA). The filters were washed under high stringency conditions and exposed at -80°C to Kodak Biomax MS-1 films (Kodak, Rochester, NY). Before blotting, 28S and 18S rRNA were stained on gels with ethidium bromide and photographed with a UV transilluminator using Polaroid positive/negative films (Polaroid, Cambridge, MA). Films were subjected to densitometry by an Imaging Densitometer model GS-670 (Bio-Rad, Richmond, CA) supported by the Quantity One software, and densitometric values were calculated by dividing the values of specific bands by the values of 28S rRNA.
Western blot analysis
Western blot analysis of tyrosine-phosphorylated STAT-1 and STAT-3 was determined in DC whole-cell lysates. In brief, DCs (2 x 107 cells/ml) were resuspended in RIPA buffer containing 1% Nonidet P-40, 0.5% sodium deoxycolate, 0.1% SDS, 1 mM sodium orthovanadate, and protease inhibitors and sheared through a 28-gauge needle. After a 30-min incubation on ice, lysates were centrifuged at 13,500 x g for 15 min and supernatants were collected. A total of 5–10 µg of proteins were subjected to 6.5% SDS-PAGE under reducing conditions and then transferred to polyvinylidene difluoride membranes (Hybond-P; Amersham). Membranes were probed with anti-phosphotyrosine STAT-1 and STAT-3 rabbit polyclonal Abs (New England Biolabs, Beverly, MA), and developed with HRP-conjugated anti-rabbit Ig (Santa Cruz Biotechnology, Santa Cruz, CA) by using the ECL-plus detection system (Amersham).
Statistics
The unpaired two-tailed Student’s t test was used to
compare differences in DC membrane markers expression, cytokines
release, and T cell proliferation, and p 
0.05 were
considered significant.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In the first series of experiments, we tested the capacity of DCs
to release IL-10 in response to different maturation signals. Fig. 1
shows that immature DCs secreted low
but sizeable amounts of IL-10 (20–50 pg/ml/106
cells). DC stimulated with Gram-negative or Gram-positive bacteria or
bacterial cell wall constituents released high levels of IL-10 (8–16
ng/ml), whereas exposure of DCs to poly I:C led to moderate IL-10
release (2–4 ng/ml). CD40 triggering with either sCD40L or
CD40L-transfected L cells (not shown) was also an efficient stimulus
for IL-10 secretion (4–5 ng/ml), although less potent than bacteria.
Treatment with anti-HLA-DR mAb had no effect on IL-10 release and
did not significantly modify cytokine secretion induced by CD40
ligation.
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and IL-12 release, reduces
IL-10 production, and augments DC maturation induced by LPS or sCD40L
To evaluate the role of endogenous IL-10 in DC cytokine
production, a neutralizing anti-IL-10 mAb was added to immature DC
cultures as well as to DCs concomitantly treated with LPS or sCD40L,
paradigmatic of the noncognate and cognate maturation signals,
respectively. Incubation of immature DCs with anti-IL-10 mAb but
not with control mouse IgG for 18 h induced a higher secretion of
TNF- (Fig. 2A). More
strikingly, a prominent augmented secretion of TNF- and IL-12 was
measured in DCs stimulated with LPS or sCD40L and concomitantly treated
with anti-IL-10 mAb, indicating that endogenous IL-10 has a strong
inhibitory effect on IL-12 and TNF- production by maturing DCs. In
contrast, IL-10 neutralization diminished by 1.5- to 2-fold the IL-10
mRNA accumulation induced by LPS or CD40 triggering as shown by
Northern blot analysis (Fig. 2C). Thus, these results
suggested that autocrine IL-10 increased its own production, extending
previously published data at the protein level (13, 14).
IL-10 protein detection could not be performed by ELISA because the
presence of the neutralizing anti-IL-10 mAb interfered with a
precise estimation of the cytokine.
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shows that immature
DCs incubated for 18 h with anti-IL-10 blocking mAb displayed
enhanced membrane levels of CD80, CD86, and CD83, suggesting that DCs
deprived of endogenous IL-10 undergo spontaneous maturation in vitro.
In addition, IL-10 neutralization further augmented the up-regulation
of CD80, CD86, CD83, and MHC molecules induced by either LPS or sCD40L.
Although IL-10 neutralization augmented membrane HLA-DR expression in
most experiments, in some cases no changes or, less frequently, slight
reduction was observed, as noted previously (11, 14, 15).
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The functional consequences of IL-10 neutralization initially were
tested in the primary MLR assay. Blocking endogenous IL-10 did not
change the capacity of immature DCs to activate allogeneic T cells
(Fig. 3A). However, DCs
matured with LPS or sCD40L in the presence of
anti-IL-10 mAb exhibited enhanced allostimulatory capacity (Fig. 3, B and C). Next, we studied the ability of DCs
treated with anti-IL-10 to direct the differentiation of naive T
cells. To this end, purified naive CD45RA+
allogeneic T cells were activated with immature or mature DCs treated
with anti-IL-10 or control IgG. After 6 days, T cells were
restimulated with plate-coated anti-CD3 and soluble anti-CD28
and analyzed for lymphokine production. T cells stimulated with
immature DCs differentiated into both Th1 and Th2 cells, whereas LPS-
or sCD40L-matured DCs induced the preferential development of Th1 cells
(Fig. 4). Addition of anti-IL-10 Ab
augmented the percentage of IFN--positive cells induced by both
immature or mature DCs. In parallel, the percentage of IL-4-positive
cells generated with immature DCs was reduced by anti-IL-10
treatment. Similar results were observed by measuring lymphokines
secreted at 48 h, where immature or mature DCs stimulated T cells
to release higher IFN- but lower IL-4 and IL-5 after endogenous
IL-10 neutralization (Fig. 5).
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Several reports have demonstrated that mature DCs become resistant
to the effects of exogenous IL-10 (14, 15, 17, 19, 20, 21).
Consistent with this notion, addition of anti-IL-10 mAb to already
matured DCs had no influence on cytokine release and surface phenotype
(data not shown). To test the sensitivity of mature DCs to IL-10, the
activation of molecules involved in the signal transduction to IL-10
was investigated. Ligation of IL-10 to its receptor leads to the
activation of Janus kinase 1 and tyrosine kinase 2, and then to
the recruitment and phosphorylation of STAT-1 and STAT-3
(25, 26, 27). Fig. 6 shows that
immature DCs exposed to IL-10 for 20 min displayed high amounts of
tyrosine-phosphorylated STAT-3 and low levels of
phosphoSTAT-1 (lane 3 vs lane
1). In contrast, LPS-matured DCs exhibited high
basal-phosphorylated STAT-3 and limited STAT-1 that were only slightly
increased by IL-10 (lane 4 vs lane 2). DCs
that received LPS together with anti-IL-10 mAb did not reduce
STAT-3 phosphorylation, possibly because LPS promoted the secretion of
other cytokines (e.g., IL-6, IL-12) which also activate STAT-3 (data
not shown).
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To gain insight into the mechanisms underlying the
unresponsiveness of mature DCs to IL-10, we examined the expression of
IL-10R during DC maturation. Immature DCs expressed similar amounts of
the mRNA for both IL-10R1 and IL-10R2 subunits. After activation with
LPS or sCD40L, the mRNA specific for the IL-10R1 but not for IL-10R2
was markedly up-regulated, with a 3- to 5-fold increase as determined
by densitometric analysis (Fig. 7A). Treatment with
anti-IL-10 increased the mRNA signals for IL-10R1 but not for
IL-10R2 in both immature and in LPS- or sCD40L-matured DCs (from 1.5-
to 3-fold increase), suggesting that endogenous IL-10 can reduce
IL-10R1 mRNA accumulation. Total IL-10R1 protein expression and IL-10
binding activity both were enhanced in mature DCs or cells treated with
anti-IL-10 mAb, paralleling the mRNA data (Fig. 7B). In
contrast, surface IL-10R1 and IL-10 binding capacity decreased in the
same conditions. ELISA confirmed that higher levels of IL-10R1 were
present in whole cell lysates from LPS-matured DCs compared with
immature DCs (930 ± 110 vs 600 ± 54 pg/ml; mean ± SD
of three experiments; p < 0.02). Finally, IL-10R1
could not be detected by ELISA in supernatants from either immature or
mature DCs, indicating that the receptor was not shed from the
membrane.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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. These findings suggest
that DCs can undergo spontaneous maturation in vitro even in the
absence of exogenous signals and that autocrine IL-10 is important in
maintaining DC in an immature state. IL-10 neutralization also was able
to reinforce DC maturation induced by LPS or CD40 triggering in terms
of phenotypic changes and cytokine production as well as
alloantigen-presenting capacity. Moreover, DCs matured in the presence
of anti-IL-10 mAb were more potent at directing Th1 differentiation
of naive T cells, clearly indicating that autocrine IL-10 also can
efficiently limit the capacity of DCs to initiate Th1 responses.
Although IL-10 neutralization increased the release of IL-12 and
TNF-, it diminished IL-10 synthesis, suggesting that autocrine IL-10
also provides a positive feedback mechanism for its own production.
Interestingly enough, primary DCs undergo spontaneous maturation in
vitro on isolation from tissues such as the skin or the spleen
(37, 38), but the mechanisms responsible have not been
defined yet. However, both human epidermal Langerhans cells and mouse
spleen DCs do not express IL-10 mRNA (39, 40), and this
may explain, at least in part, their spontaneous maturation during
short-term culture. Also, DCs generated from
CD1a+ progenitors (30) and
Langerhans cells differentiated from monocytes or
CD34+ progenitors in the presence of TGF- fail
to synthesize IL-10 (41, 42), whereas peripheral blood
CD83+ DCs express IL-10 mRNA (43).
Therefore, it appears that IL-10 production is a property of some DC
subsets. In particular, IL-10 is abundantly produced by
monocyte-derived DCs, which are paradigmatic of DCs that accumulate at
sites of chronic inflammation (44). Hence, it is possible
that these DCs are equipped with IL-10 as a potent mechanism to prevent
exaggerated or distorted (e.g., against self-Ags) immune responses. By
contrast, the lack of IL-10 in DCs that usually reside in and patrol
unperturbed tissues may be important for not rendering them insensitive
to potential danger signals and ultimately favors the induction of
protective immune responses against pathogens (45).
Alternatively, distinct DC subsets may rely on different mechanisms to
refrain from uncontrolled maturation (41). A regulatory
role for autocrine IL-10 has been described previously for monocytes
and macrophages (46, 47). Similarly to DCs, IL-10 has been
shown to inhibit the production of proinflammatory cytokines in
monocytes. However, in sharp contrast to DCs, IL-10 (both exogenous and
autocrine) also inhibited its own production in monocytes
(46). IL-10 derived from DCs can also affect DCs in a
paracrine fashion and alter the functions of other cell types. For
example, it may affect the differentiation of T lymphocytes and promote
the development of T regulatory cells or increase the effector
functions of CD8+ T cells (45).
Mature DCs lose sensitivity to IL-10, but the mechanisms of this
unresponsiveness have not been investigated. Here we found that on
exposure to IL-10, immature DCs showed high levels of
tyrosine-phosphorylated STAT-3 and low STAT-1. In contrast, mature DCs
displayed high basal-phosphorylated STAT-3 and some STAT-1 that were
only minimally increased by IL-10, suggesting an impaired early signal
transduction defect to IL-10 in mature DCs. IL-10 acts through a
heterodimeric membrane receptor formed by a binding (IL-10R1) and a
signaling subunit (IL-10R2). Both chains are required for optimal
signal transduction (22, 23). Here, we found that immature
DCs expressed comparable amounts of IL-10R1 and IL-10R2 mRNA. After
maturation, DCs up-regulated selectively the IL-10R1 mRNA, with IL-10R1
and IL-10 binding activity increased intracellularly but markedly
reduced on the surface. Similar findings were observed in immature DCs
after neutralization of endogenous IL-10, and addition of
anti-IL-10 to maturing DCs further amplified the difference between
intracellular and surface IL-10R1 expression, suggesting that
endogenous IL-10 can modulate the expression and function of its own
receptor. In agreement with our findings, a recent report showed that
rheumatoid synovial DCs, representative of mature DCs, expressed
IL-10R1 protein predominantly intracellular (21). The
reduced membrane IL-10R1 expression may be one mechanism by which
mature DCs become resistant to IL-10. Mature DCs also are unresponsive
to IFN- and down-regulate membrane IFN-R1 expression
(48). Both the IFN-R1 and IL-10R1 belong to the class
II cytokine receptor family, and share many similarities in their
structure (22, 23, 24). At the moment, it is difficult to
reconcile the finding that during maturation DCs increased IL-10R1 mRNA
and intracellular protein but reduced surface IL-10R1 and IL-10 binding
activity. Loss of membrane IL-10R1 was not attributable to receptor
shedding, as no soluble IL-10R1 could be measured in cell culture
supernatant. It is instead possible that membrane IL-10R1
down-regulation is secondary to posttranslational events such as
altered receptor trafficking and/or recycling from intracellular stores
to the cell membrane, as suggested for the chemokine receptor CCR5 in
LPS-stimulated monocytes (49).
In conclusion, our study provides evidence that autocrine IL-10 and IL-10R serve as a relevant modulatory loop for the regulation of DC maturation, with important consequences on the outcome of the immune response. Blocking IL-10 production by DCs or DC responsiveness to IL-10 may add to DC-based therapeutic strategies aimed at inducing or amplifying type 1 immunity, as recently shown in mouse models (50, 51). In contrast, an unrestricted production of IL-10 by DCs may be exploited to dampen unwanted type 1 immune responses, and indeed drugs such as corticosteroids and vitamin D3 with the ability to suppress these reactions inhibit the maturation of DCs, including IL-12 release, but do not affect or even stimulate IL-10 production (52, 53, 54, 55).
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Silvia Corinti, Laboratory of Immunology, Istituto Dermopatico dell’Immacolata, Via Monti di Creta 104, 00167 Roma, Italy.
3 Abbreviations used in this paper: DC, dendritic cell; CD40L, CD40 ligand; sCD40L, soluble CD40L; LTA, lipoteichoic acid.
Received for publication November 2, 2000. Accepted for publication January 19, 2001.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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M. Guilliams, K. Movahedi, T. Bosschaerts, T. VandenDriessche, M. K. Chuah, M. Herin, A. Acosta-Sanchez, L. Ma, M. Moser, J. A. Van Ginderachter, et al. IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection J. Immunol., January 15, 2009; 182(2): 1107 - 1118. [Abstract] [Full Text] [PDF]
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E. Henry, C. J. Desmet, V. Garze, L. Fievez, D. Bedoret, C. Heirman, P. Faisca, F. J. Jaspar, P. Gosset, A. P. A. Jacquet, et al. Dendritic Cells Genetically Engineered to Express IL-10 Induce Long-Lasting Antigen-Specific Tolerance in Experimental Asthma J. Immunol., November 15, 2008; 181(10): 7230 - 7242. [Abstract] [Full Text] [PDF]
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M.-F. Mashreghi, R. Klemz, I. S. Knosalla, B. Gerstmayer, U. Janssen, R. Buelow, A. Jozkowicz, J. Dulak, H.-D. Volk, and K. Kotsch Inhibition of Dendritic Cell Maturation and Function Is Independent of Heme Oxygenase 1 but Requires the Activation of STAT3 J. Immunol., June 15, 2008; 180(12): 7919 - 7930. [Abstract] [Full Text] [PDF]
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L. Flores-Mendoza, E. Silva-Campa, M. Resendiz, F. A. Osorio, and J. Hernandez Porcine Reproductive and Respiratory Syndrome Virus Infects Mature Porcine Dendritic Cells and Up-Regulates Interleukin-10 Production Clin. Vaccine Immunol., April 1, 2008; 15(4): 720 - 725. [Abstract] [Full Text] [PDF]
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S. Gaudreau, C. Guindi, M. Menard, G. Besin, G. Dupuis, and A. Amrani Granulocyte-Macrophage Colony-Stimulating Factor Prevents Diabetes Development in NOD Mice by Inducing Tolerogenic Dendritic Cells that Sustain the Suppressive Function of CD4+CD25+ Regulatory T Cells J. Immunol., September 15, 2007; 179(6): 3638 - 3647. [Abstract] [Full Text] [PDF]
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G. Perona-Wright, S. M. Anderton, S. E. M. Howie, and D. Gray IL-10 permits transient activation of dendritic cells to tolerize T cells and protect from central nervous system autoimmune disease Int. Immunol., September 1, 2007; 19(9): 1123 - 1134. [Abstract] [Full Text] [PDF]
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W. E. Walker and D. R. Goldstein Neonatal B Cells Suppress Innate Toll-Like Receptor Immune Responses and Modulate Alloimmunity J. Immunol., August 1, 2007; 179(3): 1700 - 1710. [Abstract] [Full Text] [PDF]
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L. Barrett, C. Dai, J. Gamberg, M. Gallant, and M. Grant Circulating CD14-CD36+ peripheral blood mononuclear cells constitutively produce interleukin-10 J. Leukoc. Biol., July 1, 2007; 82(1): 152 - 160. [Abstract] [Full Text] [PDF]
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W. L. W. Chang, N. Baumgarth, M. K. Eberhardt, C. Y. D. Lee, C. A. Baron, J. P. Gregg, and P. A. Barry Exposure of Myeloid Dendritic Cells to Exogenous or Endogenous IL-10 during Maturation Determines Their Longevity J. Immunol., June 15, 2007; 178(12): 7794 - 7804. [Abstract] [Full Text] [PDF]
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A. S. Hatzfeld-Charbonnier, A. Lasek, L. Castera, P. Gosset, T. Velu, P. Formstecher, L. Mortier, and P. Marchetti Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines J. Leukoc. Biol., May 1, 2007; 81(5): 1179 - 1187. [Abstract] [Full Text] [PDF]
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R. R. Flores, K. A. Diggs, L. M. Tait, and P. A. Morel IFN-{gamma} Negatively Regulates CpG-Induced IL-10 in Bone Marrow-Derived Dendritic Cells J. Immunol., January 1, 2007; 178(1): 211 - 218. [Abstract] [Full Text] [PDF]
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D. Braun, L. Galibert, T. Nakajima, H. Saito, V. V. Quang, M. Rubio, and M. Sarfati Semimature Stage: A Checkpoint in a Dendritic Cell Maturation Program That Allows for Functional Reversion after Signal-Regulatory Protein-{alpha} Ligation and Maturation Signals J. Immunol., December 15, 2006; 177(12): 8550 - 8559. [Abstract] [Full Text] [PDF]
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S. Wang, S. Hong, J. Yang, J. Qian, X. Zhang, E. Shpall, L. W. Kwak, and Q. Yi Optimizing immunotherapy in multiple myeloma: restoring the function of patients' monocyte-derived dendritic cells by inhibiting p38 or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells Blood, December 15, 2006; 108(13): 4071 - 4077. [Abstract] [Full Text] [PDF]
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Y. Y. Lan, Z. Wang, G. Raimondi, W. Wu, B. L. Colvin, A. De Creus, and A. W. Thomson "Alternatively Activated" Dendritic Cells Preferentially Secrete IL-10, Expand Foxp3+CD4+ T Cells, and Induce Long-Term Organ Allograft Survival in Combination with CTLA4-Ig J. Immunol., November 1, 2006; 177(9): 5868 - 5877. [Abstract] [Full Text] [PDF]
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X. S. Liu, J. Dyer, G. R. Leggatt, G. J. P. Fernando, J. Zhong, R. Thomas, and I. H. Frazer Overcoming Original Antigenic Sin to Generate New CD8 T Cell IFN-{gamma} Responses in an Antigen-Experienced Host. J. Immunol., September 1, 2006; 177(5): 2873 - 2879. [Abstract] [Full Text] [PDF]
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Y. Li, N. Chu, A. Rostami, and G.-X. Zhang Dendritic Cells Transduced with SOCS-3 Exhibit a Tolerogenic/DC2 Phenotype That Directs Type 2 Th Cell Differentiation In Vitro and In Vivo J. Immunol., August 1, 2006; 177(3): 1679 - 1688. [Abstract] [Full Text] [PDF]
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M. Severa, M. E. Remoli, E. Giacomini, J. Ragimbeau, R. Lande, G. Uze, S. Pellegrini, and E. M. Coccia Differential responsiveness to IFN-{alpha} and IFN-{beta} of human mature DC through modulation of IFNAR expression J. Leukoc. Biol., June 1, 2006; 79(6): 1286 - 1294. [Abstract] [Full Text] [PDF]
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M. Veldhoen, H. Moncrieffe, R. J. Hocking, C. J. Atkins, and B. Stockinger Modulation of Dendritic Cell Function by Naive and Regulatory CD4+ T Cells J. Immunol., May 15, 2006; 176(10): 6202 - 6210. [Abstract] [Full Text] [PDF]
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M. Kramer, M. G. Netea, D. J. de Jong, B. J. Kullberg, and G. J. Adema Impaired dendritic cell function in Crohn's disease patients with NOD2 3020insC mutation J. Leukoc. Biol., April 1, 2006; 79(4): 860 - 866. [Abstract] [Full Text] [PDF]
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S. B. Flohe, H. Agrawal, D. Schmitz, M. Gertz, S. Flohe, and F. U. Schade Dendritic cells during polymicrobial sepsis rapidly mature but fail to initiate a protective Th1-type immune response J. Leukoc. Biol., March 1, 2006; 79(3): 473 - 481. [Abstract] [Full Text] [PDF]
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W. Vermi, F. Facchetti, E. Riboldi, H. Heine, S. Scutera, S. Stornello, D. Ravarino, P. Cappello, M. Giovarelli, R. Badolato, et al. Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma Blood, January 15, 2006; 107(2): 454 - 462. [Abstract] [Full Text] [PDF]
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M. T. Rubio, T. K. Means, R. Chakraverty, J. Shaffer, Y. Fudaba, M. Chittenden, A. D. Luster, and M. Sykes Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs Int. Immunol., December 1, 2005; 17(12): 1561 - 1572. [Abstract] [Full Text] [PDF]
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T. K. Varma, M. Durham, E. D. Murphey, W. Cui, Z. Huang, C. Y. Lin, T. Toliver-Kinsky, and E. R. Sherwood Endotoxin Priming Improves Clearance of Pseudomonas aeruginosa in Wild-Type and Interleukin-10 Knockout Mice Infect. Immun., November 1, 2005; 73(11): 7340 - 7347. [Abstract] [Full Text] [PDF]
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S. Mocellin, F. M. Marincola, and H. A. Young Interleukin-10 and the immune response against cancer: a counterpoint J. Leukoc. Biol., November 1, 2005; 78(5): 1043 - 1051. [Abstract] [Full Text] [PDF]
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D. S. Pouniotis, O. Proudfoot, V. Bogdanoska, K. Scalzo, S. Kovacevic, R. L. Coppel, and M. Plebanski Selectively Impaired CD8+ but Not CD4+ T Cell Cycle Arrest during Priming as a Consequence of Dendritic Cell Interaction with Plasmodium-Infected Red Cells J. Immunol., September 15, 2005; 175(6): 3525 - 3533. [Abstract] [Full Text] [PDF]
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L. Freeman, M. Hewison, S. V. Hughes, K. N. Evans, D. Hardie, T. K. Means, and R. Chakraverty Expression of 11{beta}-hydroxysteroid dehydrogenase type 1 permits regulation of glucocorticoid bioavailability by human dendritic cells Blood, September 15, 2005; 106(6): 2042 - 2049. [Abstract] [Full Text] [PDF]
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D. McIlroy, S. Tanguy-Royer, N. Le Meur, I. Guisle, P.-J. Royer, J. Leger, K. Meflah, and M. Gregoire Profiling dendritic cell maturation with dedicated microarrays J. Leukoc. Biol., September 1, 2005; 78(3): 794 - 803. [Abstract] [Full Text] [PDF]
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S. Iwamoto, M. Ishida, K. Takahashi, K. Takeda, and A. Miyazaki Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs) to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell responses J. Leukoc. Biol., August 1, 2005; 78(2): 383 - 392. [Abstract] [Full Text] [PDF]
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A. Rughetti, I. Pellicciotta, M. Biffoni, M. Backstrom, T. Link, E. P. Bennet, H. Clausen, T. Noll, G. C. Hansson, J. M. Burchell, et al. Recombinant Tumor-Associated MUC1 Glycoprotein Impairs the Differentiation and Function of Dendritic Cells J. Immunol., June 15, 2005; 174(12): 7764 - 7772. [Abstract] [Full Text] [PDF]
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K. B. Gurney, J. Elliott, H. Nassanian, C. Song, E. Soilleux, I. McGowan, P. A. Anton, and B. Lee Binding and Transfer of Human Immunodeficiency Virus by DC-SIGN+ Cells in Human Rectal Mucosa J. Virol., May 1, 2005; 79(9): 5762 - 5773. [Abstract] [Full Text] [PDF]
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S. S. Kang and P. M. Allen Priming in the Presence of IL-10 Results in Direct Enhancement of CD8+ T Cell Primary Responses and Inhibition of Secondary Responses J. Immunol., May 1, 2005; 174(9): 5382 - 5389. [Abstract] [Full Text] [PDF]
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G. Fedele, P. Stefanelli, F. Spensieri, C. Fazio, P. Mastrantonio, and C. M. Ausiello Bordetella pertussis-Infected Human Monocyte-Derived Dendritic Cells Undergo Maturation and Induce Th1 Polarization and Interleukin-23 Expression Infect. Immun., March 1, 2005; 73(3): 1590 - 1597. [Abstract] [Full Text] [PDF]
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A. P. Smith, C. Paolucci, G. Di Lullo, S. E. Burastero, F. Santoro, and P. Lusso Viral Replication-Independent Blockade of Dendritic Cell Maturation and Interleukin-12 Production by Human Herpesvirus 6 J. Virol., March 1, 2005; 79(5): 2807 - 2813. [Abstract] [Full Text] [PDF]
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M. K. Levings, S. Gregori, E. Tresoldi, S. Cazzaniga, C. Bonini, and M. G. Roncarolo Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells Blood, February 1, 2005; 105(3): 1162 - 1169. [Abstract] [Full Text] [PDF]
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G. Grutz New insights into the molecular mechanism of interleukin-10-mediated immunosuppression J. Leukoc. Biol., January 1, 2005; 77(1): 3 - 15. [Abstract] [Full Text] [PDF]
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M. Peiser, R. Wanner, and G. Kolde Human epidermal Langerhans cells differ from monocyte-derived Langerhans cells in CD80 expression and in secretion of IL-12 after CD40 cross-linking J. Leukoc. Biol., September 1, 2004; 76(3): 616 - 622. [Abstract] [Full Text] [PDF]
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S. Chang-Rodriguez, R. Ecker, G. Stingl, and A. Elbe-Burger Autocrine IL-10 partially prevents differentiation of neonatal dendritic epidermal leukocytes into Langerhans cells J. Leukoc. Biol., September 1, 2004; 76(3): 657 - 666. [Abstract] [Full Text] [PDF]
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X. Chen, K. Doffek, S. L. Sugg, and J. Shilyansky Phosphatidylserine Regulates the Maturation of Human Dendritic Cells J. Immunol., September 1, 2004; 173(5): 2985 - 2994. [Abstract] [Full Text] [PDF]
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M. J. Raftery, D. Wieland, S. Gronewald, A. A. Kraus, T. Giese, and G. Schonrich Shaping Phenotype, Function, and Survival of Dendritic Cells by Cytomegalovirus-Encoded IL-10 J. Immunol., September 1, 2004; 173(5): 3383 - 3391. [Abstract] [Full Text] [PDF]
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P. Mandrekar, D. Catalano, A. Dolganiuc, K. Kodys, and G. Szabo Inhibition of Myeloid Dendritic Cell Accessory Cell Function and Induction of T Cell Anergy by Alcohol Correlates with Decreased IL-12 Production J. Immunol., September 1, 2004; 173(5): 3398 - 3407. [Abstract] [Full Text] [PDF]
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W. L. W. Chang, N. Baumgarth, D. Yu, and P. A. Barry Human Cytomegalovirus-Encoded Interleukin-10 Homolog Inhibits Maturation of Dendritic Cells and Alters Their Functionality J. Virol., August 15, 2004; 78(16): 8720 - 8731. [Abstract] [Full Text] [PDF]
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S. Bhattacharyya, P. Sen, M. Wallet, B. Long, A. S. Baldwin Jr, and R. Tisch Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of I{kappa}B kinase activity Blood, August 15, 2004; 104(4): 1100 - 1109. [Abstract] [Full Text] [PDF]
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M. Kurte, M. Lopez, A. Aguirre, A. Escobar, J. C. Aguillon, J. Charo, C. G. Larsen, R. Kiessling, and F. Salazar-Onfray A Synthetic Peptide Homologous to Functional Domain of Human IL-10 Down-Regulates Expression of MHC Class I and Transporter Associated with Antigen Processing 1/2 in Human Melanoma Cells J. Immunol., August 1, 2004; 173(3): 1731 - 1737. [Abstract] [Full Text] [PDF]
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D. Avigan, B. Vasir, J. Gong, V. Borges, Z. Wu, L. Uhl, M. Atkins, J. Mier, D. McDermott, T. Smith, et al. Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses Clin. Cancer Res., July 15, 2004; 10(14): 4699 - 4708. [Abstract] [Full Text] [PDF]
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C. Carbonneil, H. Saidi, V. Donkova-Petrini, and L. Weiss Dendritic cells generated in the presence of interferon-{alpha} stimulate allogeneic CD4+ T-cell proliferation: modulation by autocrine IL-10, enhanced T-cell apoptosis and T regulatory type 1 cells Int. Immunol., July 1, 2004; 16(7): 1037 - 1052. [Abstract] [Full Text] [PDF]
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C. Carbonneil, V. Donkova-Petrini, A. Aouba, and L. Weiss Defective Dendritic Cell Function in HIV-Infected Patients Receiving Effective Highly Active Antiretroviral Therapy: Neutralization of IL-10 Production and Depletion of CD4+CD25+ T Cells Restore High Levels of HIV-Specific CD4+ T Cell Responses Induced by Dendritic Cells Generated in the Presence of IFN-{alpha} J. Immunol., June 15, 2004; 172(12): 7832 - 7840. [Abstract] [Full Text] [PDF]
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P. Perrier, F. O. Martinez, M. Locati, G. Bianchi, M. Nebuloni, G. Vago, F. Bazzoni, S. Sozzani, P. Allavena, and A. Mantovani Distinct Transcriptional Programs Activated by Interleukin-10 with or without Lipopolysaccharide in Dendritic Cells: Induction of the B Cell-Activating Chemokine, CXC Chemokine Ligand 13 J. Immunol., June 1, 2004; 172(11): 7031 - 7042. [Abstract] [Full Text] [PDF]
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N. Misra, J. Bayry, S. Lacroix-Desmazes, M. D. Kazatchkine, and S. V. Kaveri Cutting Edge: Human CD4+CD25+ T Cells Restrain the Maturation and Antigen-Presenting Function of Dendritic Cells J. Immunol., April 15, 2004; 172(8): 4676 - 4680. [Abstract] [Full Text] [PDF]
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J. H. Edwan, G. Perry, J. E. Talmadge, and D. K. Agrawal Flt-3 Ligand Reverses Late Allergic Response and Airway Hyper-Responsiveness in a Mouse Model of Allergic Inflammation J. Immunol., April 15, 2004; 172(8): 5016 - 5023. [Abstract] [Full Text] [PDF]
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S.-F. Wu, T.-M. Liu, Y.-C. Lin, H.-K. Sytwu, H.-F. Juan, S.-T. Chen, K.-L. Shen, S.-C. Hsi, and S.-L. Hsieh Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory mechanism to clinical implication J. Leukoc. Biol., February 1, 2004; 75(2): 293 - 306. [Abstract] [Full Text] [PDF]
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S. Goddard, J. Youster, E. Morgan, and D. H. Adams Interleukin-10 Secretion Differentiates Dendritic Cells from Human Liver and Skin Am. J. Pathol., February 1, 2004; 164(2): 511 - 519. [Abstract] [Full Text] [PDF]
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S. Fontana, D. Moratto, S. Mangal, M. De Francesco, W. Vermi, S. Ferrari, F. Facchetti, N. Kutukculer, C. Fiorini, M. Duse, et al. Functional defects of dendritic cells in patients with CD40 deficiency Blood, December 1, 2003; 102(12): 4099 - 4106. [Abstract] [Full Text] [PDF]
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J. Colino and C. M. Snapper Opposing Signals from Pathogen-Associated Molecular Patterns and IL-10 Are Critical for Optimal Dendritic Cell Induction of In Vivo Humoral Immunity to Streptococcus pneumoniae J. Immunol., October 1, 2003; 171(7): 3508 - 3519. [Abstract] [Full Text] [PDF]
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E. C. Lavelle, E. McNeela, M. E. Armstrong, O. Leavy, S. C. Higgins, and K. H. G. Mills Cholera Toxin Promotes the Induction of Regulatory T Cells Specific for Bystander Antigens by Modulating Dendritic Cell Activation J. Immunol., September 1, 2003; 171(5): 2384 - 2392. [Abstract] [Full Text] [PDF]
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R. Morita, N. Ukyo, M. Furuya, T. Uchiyama, and T. Hori Atrial Natriuretic Peptide Polarizes Human Dendritic Cells Toward a Th2-Promoting Phenotype Through Its Receptor Guanylyl Cyclase-Coupled Receptor A J. Immunol., June 15, 2003; 170(12): 5869 - 5875. [Abstract] [Full Text] [PDF]
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M. Hewison, L. Freeman, S. V. Hughes, K. N. Evans, R. Bland, A. G. Eliopoulos, M. D. Kilby, P. A. H. Moss, and R. Chakraverty Differential Regulation of Vitamin D Receptor and Its Ligand in Human Monocyte-Derived Dendritic Cells J. Immunol., June 1, 2003; 170(11): 5382 - 5390. [Abstract] [Full Text] [PDF]
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A. Dolganiuc, K. Kodys, A. Kopasz, C. Marshall, T. Do, L. Romics Jr., P. Mandrekar, M. Zapp, and G. Szabo Hepatitis C Virus Core and Nonstructural Protein 3 Proteins Induce Pro- and Anti-inflammatory Cytokines and Inhibit Dendritic Cell Differentiation J. Immunol., June 1, 2003; 170(11): 5615 - 5624. [Abstract] [Full Text] [PDF]
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A. M. Woltman and C. van Kooten Functional modulation of dendritic cells to suppress adaptive immune responses J. Leukoc. Biol., April 1, 2003; 73(4): 428 - 441. [Abstract] [Full Text] [PDF]
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J.-N. Tournier, A. Q. Hellmann, G. Lesca, A. Jouan, E. Drouet, and J. Mathieu Fever-like thermal conditions regulate the activation of maturing dendritic cells J. Leukoc. Biol., April 1, 2003; 73(4): 493 - 501. [Abstract] [Full Text] [PDF]
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G. Miller, V. G. Pillarisetty, A. B. Shah, S. Lahrs, and R. P. DeMatteo Murine Flt3 Ligand Expands Distinct Dendritic Cells with Both Tolerogenic and Immunogenic Properties J. Immunol., April 1, 2003; 170(7): 3554 - 3564. [Abstract] [Full Text] [PDF]
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M. Vulcano, S. Struyf, P. Scapini, M. Cassatella, S. Bernasconi, R. Bonecchi, A. Calleri, G. Penna, L. Adorini, W. Luini, et al. Unique Regulation of CCL18 Production by Maturing Dendritic Cells J. Immunol., April 1, 2003; 170(7): 3843 - 3849. [Abstract] [Full Text] [PDF]
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S. Sharma, M. Stolina, S.-C. Yang, F. Baratelli, J. F. Lin, K. Atianzar, J. Luo, L. Zhu, Y. Lin, M. Huang, et al. Tumor Cyclooxygenase 2-dependent Suppression of Dendritic Cell Function Clin. Cancer Res., March 1, 2003; 9(3): 961 - 968. [Abstract] [Full Text] [PDF]
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N. Heuze-Vourc'h, L. Zhu, K. Krysan, R. K. Batra, S. Sharma, and S. M. Dubinett Abnormal Interleukin 10R{alpha} Expression Contributes to the Maintenance of Elevated Cyclooxygenase-2 in Non-Small Cell Lung Cancer Cells Cancer Res., February 15, 2003; 63(4): 766 - 770. [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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 K. G. Brinker, H. Garner, and J. R. Wright Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L232 - L241. [Abstract] [Full Text] [PDF]
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T. Fumeaux and J. Pugin Role of Interleukin-10 in the Intracellular Sequestration of Human Leukocyte Antigen-DR in Monocytes during Septic Shock Am. J. Respir. Crit. Care Med., December 1, 2002; 166(11): 1475 - 1482. [Abstract] [Full Text] [PDF]
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M. C. Gauzzi, I. Canini, P. Eid, F. Belardelli, and S. Gessani Loss of Type I IFN Receptors and Impaired IFN Responsiveness During Terminal Maturation of Monocyte-Derived Human Dendritic Cells J. Immunol., September 15, 2002; 169(6): 3038 - 3045. [Abstract] [Full Text] [PDF]
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S. C. Fausch, D. M. Da Silva, M. P. Rudolf, and W. M. Kast Human Papillomavirus Virus-Like Particles Do Not Activate Langerhans Cells: A Possible Immune Escape Mechanism Used by Human Papillomaviruses J. Immunol., September 15, 2002; 169(6): 3242 - 3249. [Abstract] [Full Text] [PDF]
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M. E. H. Bashir, P. Andersen, I. J. Fuss, H. N. Shi, and C. Nagler-Anderson An Enteric Helminth Infection Protects Against an Allergic Response to Dietary Antigen J. Immunol., September 15, 2002; 169(6): 3284 - 3292. [Abstract] [Full Text] [PDF]
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B. J. O'Sullivan and R. Thomas CD40 Ligation Conditions Dendritic Cell Antigen-Presenting Function Through Sustained Activation of NF-{kappa}B J. Immunol., June 1, 2002; 168(11): 5491 - 5498. [Abstract] [Full Text] [PDF]
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A. Oberholzer, C. Oberholzer, K. S. Bahjat, R. Ungaro, C. L. Tannahill, M. Murday, F. R. Bahjat, Z. Abouhamze, V. Tsai, D. LaFace, et al. Increased Survival in Sepsis by In Vivo Adenovirus-Induced Expression of IL-10 in Dendritic Cells J. Immunol., April 1, 2002; 168(7): 3412 - 3418. [Abstract] [Full Text] [PDF]
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H. Harizi, M. Juzan, V. Pitard, J.-F. Moreau, and N. Gualde Cyclooxygenase-2-Issued Prostaglandin E2 Enhances the Production of Endogenous IL-10, Which Down-Regulates Dendritic Cell Functions J. Immunol., March 1, 2002; 168(5): 2255 - 2263. [Abstract] [Full Text] [PDF]
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L. M. Stuart, M. Lucas, C. Simpson, J. Lamb, J. Savill, and A. Lacy-Hulbert Inhibitory Effects of Apoptotic Cell Ingestion upon Endotoxin-Driven Myeloid Dendritic Cell Maturation J. Immunol., February 15, 2002; 168(4): 1627 - 1635. [Abstract] [Full Text] [PDF]
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C.-Q. Xia and K.-J. Kao Heparin Induces Differentiation of CD1a+ Dendritic Cells from Monocytes: Phenotypic and Functional Characterization J. Immunol., February 1, 2002; 168(3): 1131 - 1138. [Abstract] [Full Text] [PDF]
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 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
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M. Menges, S. Ro{beta}ner, C. Voigtlander, H. Schindler, N. A. Kukutsch, C. Bogdan, K. Erb, G. Schuler, and M. B. Lutz Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor {alpha} Induce Antigen-specific Protection of Mice from Autoimmunity J. Exp. Med., December 31, 2001; 195(1): 15 - 22. [Abstract] [Full Text] [PDF]
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G. Pietra, R. Mortarini, G. Parmiani, and A. Anichini Phases of Apoptosis of Melanoma Cells, but not of Normal Melanocytes, Differently Affect Maturation of Myeloid Dendritic Cells Cancer Res., November 1, 2001; 61(22): 8218 - 8226. [Abstract] [Full Text] [PDF]
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R. A. Silva, T. F. Pais, and R. Appelberg Blocking the Receptor for IL-10 Improves Antimycobacterial Chemotherapy and Vaccination J. Immunol., August 1, 2001; 167(3): 1535 - 1541. [Abstract] [Full Text] [PDF]
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