| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
+ and CD8- Dendritic Cells to Prime Th1/Th2 Cells In Vivo1
*
Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium; and
Immunex Corporation, Seattle, WA 98101
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
- DC induces a Th2-type response, whereas
injection of CD8+ DC leads to Th1 differentiation. To
define the DC-derived factors involved in the polarization of Th
responses, we injected either subset purified from mice genetically
deficient for IFN-
, IL-4, IL-12, or IL-10 into wild-type animals. In
this work, we report that DC-derived IL-12 and IFN- are required for
Th1 priming by CD8+ DC, whereas IL-10 is required for
optimal development of Th2 cells by CD8- DC. The level
of IL-12 produced by the DC appears to determine the Th1/Th2 balance in
vivo. We further show that the function of DC subsets displays some
flexibility. Treatment of DC with IL-10 in vitro induces a selective
decrease in the viability of CD8+ DC. Conversely,
incubation with IFN- down-regulates the Th2-promoting capacities of
CD8- DC and increases the Th1-skewing properties of
both subsets. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The finding that distinct subsets of DC may differentially regulate the
development of Th1 vs Th2 cells in vivo has complicated the issue
(8, 9, 10, 11). In the mouse, we and others have shown that
adoptive transfer of Ag-pulsed CD8+ DC induces
a Th1 response, whereas injection of CD8- DC
leads to Th2 differentiation. In humans, DC are also phenotypically and
functionally heterogeneous. Plasmacytoid-derived DC induce a Th2
polarization of allogeneic naive T cells, whereas monocyte-derived DC
induce Th1 development in the same conditions (12). The
existence of DC displaying predetermined Th1- or Th2-prone capacity is
intriguing, as it may lack the flexibility required to react adequately
to a given pathogen infecting a given tissue. This paradigm prompted us
to identify the DC-derived factors that determine the Th1/Th2
polarizing properties of murine DC subsets and to assess their
functional flexibility in vitro and in vivo.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
BALB/c mice, 6–9 wk old, were purchased from Harlan Nederland
(Horst, The Netherlands). C57BL/10 mice were purchased from Harlan or
from The Jackson Laboratory (Bar Harbor, ME).
IL-12p40-/- BALB/c mice were kindly provided by
Dr. J. Magram (Hoffmann-LaRoche, Nutley, NJ).
IL-4-/- and IFN--/-
BALB/c mice and IL-10-/- C57BL/10 mice were
purchased from The Jackson Laboratory, bred in our pathogen-free
facility, and used at 6–9 wk of age. All experiments were performed in
compliance with the relevant laws and institutional guidelines, and
have been approved by the local Committee from the Institute de
Biologie et Médecine Moléculaires from the Université
Libre de Bruxelles.
Reagents and Abs
Keyhole limpet hemocyanin (KLH) was purchased from Calbiochem
(La Jolla, CA). The mAbs used were 53–6.7 (rat anti-CD8 IgG2a),
N418 (hamster anti-CD11c), JES5-2A5 (rat anti-mIL-10 IgG1) and
GL-1 (rat anti-CD86 IgG2a). Murine rIFN- and IL-10 were
purchased from PeproTech (Rocky Hill, NJ). Propidium iodide was
purchased from Sigma-Aldrich (St. Louis, MO).
Purification of DC
Mice were injected i.p. with 10 µg of recombinant human
Fms–like tyrosine kinase 3 ligand (human Chinese hamster ovary
cell-derived; produced at Immunex, Seattle, WA) for 9 consecutive days.
Splenic DC were purified by a modified procedure of a previously
described protocol (13). Briefly, spleen cells were
digested with collagenase, further dissociated in
Ca2+-free medium, separated into low- and
high-density fraction on a Nycodenz gradient (Nycomed, Oslo, Norway),
and cultured in RPMI 1640 containing 2% Ultroser HY (Life
Technologies, Paisley, Scotland). Nonadherent cells were eliminated by
vigorous pipetting. Adherent cells were cultured overnight with Ag (30
µg/ml KLH). In some experiments, rIFN- or rIL-10 (20 ng/ml) was
added during the overnight culture. The enriched DC were separated
according to CD8 expression by incubation with
anti-CD8-coupled microbeads followed by several passages over a
MACS column (Miltenyi Biotec, Bergisch-Gladbach, Germany). The
CD8- cells were further enriched for DC by
incubation with anti-CD11c-coupled microbeads and positive
selection over MACS column.
Immunization protocol
Ag-pulsed DC were washed in PBS and administered at a dose of 3 x 105 cells into the hind footpads. Draining popliteal lymph nodes were harvested 5 days later.
In vitro assays
Lymph node cells were cultured in Click’s medium supplemented
with 0.5% heat-inactivated mouse serum and additives. Culture
supernatants were assayed for IFN- and IL-4 after 72 h, and for
IL-5 and IL-10 after 96 h of incubation. IFN- and IL-10 were
measured as described (14). IL-4 and IL-5 were measured
using two-site ELISAs from BD PharMingen (San Diego, CA). The detection
limits were: 1 ng/ml for IFN-, 15 pg/ml for IL-4, 2 U/ml for IL-5,
and 0.3 ng/ml for IL-10.
Induction of IL-12 from DC subsets
Low-density spleen cells (see above) were enriched for CD11c
expression and further separated according to CD8 expression using a
Multisort anti-FITC kit (Miltenyi Biotec). Cells were cultured
overnight with or without 20 µg/ml pansorbin
(Gram- Staphylococcus
aureus cowan 1 strain; Calbiochem, La Jolla, CA), murine
rIFN-, and/or IL-10. Supernatants were assayed for IL-12p70 using
ELISA from BD PharMingen. The detection limit was 8 pg/ml.
DNA content assays
Cells were first labeled with biotinylated anti-CD8 Ab
followed by avidin-FITC. Cells were fixed with a 70% ethanol solution
for 45 min at 4°C, washed, and incubated for 40 min in 1 mg/ml RNase
solution (Sigma-Aldrich) containing 100 µg/ml of propidium iodide.
Cells were gated according to CD8 expression and analyzed for FL-2
expression in a linear scale.
DNA fragmentation assays
Cells were labeled with anti-CD8-PE, fixed with
paraformaldehyde, washed, fixed with ethanol, and further stained with
TUNEL using APO-BRDU kit from BD PharMingen. Cells were gated according
to CD8 expression and analyzed by flow cytometry.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In an effort to identify putative Th cell polarizing factors,
either produced by DC themselves or present in the microenvironment, we
analyzed the immune responses induced by adoptive transfer of DC
subsets from mice genetically deficient for selected cytokines.
Consistent with previous reports (8, 9), administration of
KLH-pulsed CD8+ DC to naive animals induced
Th1-type cytokine secretion profile, whereas injection of
CD8- DC favored Th2 development (Fig. 1
). Donor-derived IL-12 and IFN- are
both required for Th1 development, as injection of
CD8+ DC from IL-12-/-
(15) or IFN--/- mice primed for
IL-4, IL-5, and IL-10, but not IFN-, production (Fig. 1, left
panel, and data not shown). By contrast, the absence of IL-4 or
IL-10 did not affect the amplitude or the character of the immune
response induced by CD8+ DC. Injection of
CD8- DC from wild-type (WT), IL-4-, IFN--,
or IL-12-deficient mice induced similar Th2-type responses in WT
recipients (Fig. 1, right panel). Of note,
CD8- DC from IL-10 knockout (KO) mice have an
increased capacity to sensitize IFN--producing cells and a decreased
capacity to prime Th2 cells, as compared with cells from WT animals,
suggesting that IL-10 is required for optimal Th2 development.
|
It is interesting that the development of Th1 cells vs Th2 cells
appears reciprocally regulated in all groups of DC recipients (Fig. 1
),
suggesting that the different DC subsets produce factors that have
opposing effects on Th differentiation. Because IL-12 has been shown to
be a potent activator of Th1 development (1, 16), we
measured the level of bioactive IL-12p70 produced by DC from WT,
IFN--/-, and
IL-10-/- mice. The data in Fig. 2 show that
CD8+, but not CD8-,
DC from BALB/c and C57BL/10 mice produce IL-12p70 in vitro upon
stimulation with S. aureus, consistent with previous
observations. CD8+ DC from IFN--deficient
mice do not produce any detectable IL-12 under the same conditions,
unless IFN- is added to the culture. Of note, disruption of IL-10
leads to production of IL-12 heterodimer by both subsets of DC.
Conversely, addition of mouse rIL-10 prevents the secretion of IL-12 by
either subset, even in the presence of exogenous IFN-. These
observations suggest that IFN- and IL-10 inversely regulate the
production of IL-12 by DC in vivo, leading to differential induction of
Th responses.
|
or IL-10 affects their in
vivo function
We next tested whether treatment of CD8+
or CD8- DC with cytokines, which have been
shown to have opposite effects on IL-12 production (1, 7, 14), would influence their capacity to induce the development of
selected Th cell populations. Murine rIFN- or rIL-10 was added, with
Ag, during overnight culture, at a time when DC spontaneously undergo a
process of maturation (17), i.e., shift from an
Ag-capturing mode to a T cell-sensitizing mode. The various DC
populations were injected into the footpads of syngeneic mice and the
draining lymph nodes were harvested 5 days later. As shown in Fig. 3, treatment with IFN- enhanced the
Th1-promoting capacity of either subset, and diminished the capacity of
CD8- DC to induce IL-5 and IL-10
production.
|
-treated CD8+ DC from
IL-12-deficient mice induced the development of cells producing
IFN-, IL-4, IL-5, and IL-10, suggesting that their capacity to prime
for Th1 is at least partially IL-12 independent.
Treatment of CD8- DC with IL-10 resulted in
enhanced Th2 priming. Unexpectedly, incubation with IL-10
down-regulated the Ag-presenting capacity of
CD8+ DC, as assessed by the low proliferation
and cytokine production by lymph node cells upon antigenic
restimulation in vitro. The weak immune response induced by
IL-10-treated CD8+ DC prompted us to analyze
the phenotype of DC subsets after overnight culture. Triple staining
for CD11c, CD8, and CD86 revealed a selective loss of
CD8+ DC following incubation with IL-10 (Fig. 4, left panel), which is
prevented by the addition of neutralizing Abs. The loss of
CD8+ DC is likely to result from cell death,
as these cells scored positive for propidium iodide after 16–18 h of
culture with IL-10 (Fig. 4, cell viability). Percentage of apoptotic
cells was assessed by cytofluorometric analysis of DNA content and
fragmentation in permeabilized cells (Fig. 4). Spontaneous apoptosis of
CD8+ DC after 6–8 h of culture was 
8%, as
assessed by DNA content assay, whereas pretreatment with IL-10
increased the proportion of apoptotic cells to 29% (Fig. 4, DNA
content). The percentage of apoptotic CD8- DC
remained unchanged under the same conditions. Similarly, incubation
with IL-10 resulted in increased numbers of TUNEL-positive
CD8+ DC (Fig. 4, right panel).
Collectively, these data indicate that IFN- and IL-10 profoundly
affect the function of DC subclasses, and that the regulatory role of
IL-10 may involve a differential control of subset survival.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
+ and CD8- DC and
show that their function is tightly regulated by endogenous and
microenvironmental cytokines.
Our observations suggest that the level of IL-12 produced by the DC
determines the Th1/Th2 balance in vivo, with high amounts favoring a
polarized Th1-type response, intermediate amounts a mixed Th1/Th2-type
response, and low amounts a polarized Th2-type response. It should be
noted that the data presented herein represent the overall Ag-specific
immune response. Although we have shown previously that the
KLH-specific response is dependent on CD4+ T
lymphocytes (8), other cell populations may contribute to
cytokine production. Additional studies, including intracellular
cytokine staining, will be required to clarify this point. Accumulating
evidence has indicated that CD8+ DC are the
major IL-12-producing cells in vitro and in vivo. Toxoplasma
gondii products stimulate IL-12 production by
CD8+ in mice by a CCR5-dependent mechanism
(18, 19). Stimulation of CD8+,
but not CD8-, DC with S. aureus in
vitro induces IL-12 production (Refs. 8 , 11 ,
and this paper). However, the results presented herein show that
CD8- DC also have the capacity to secrete
IL-12, but that IL-10 exerts a negative immunoregulatory influence on
this production. Similarly, Reis e Sousa et al. (20) have
reported that CD8- DC can make IL-12 after in
vivo priming. The observation that CD8+ DC, in
contrast to CD8- DC and macrophages, can
produce IL-12 as early as 1 h after in vivo stimulation and in the
apparent absence of any priming, suggests that
CD8+ DC may be the major IL-12 producers in
the earliest stages of the immune response.
CD8- DC and macrophages may play a role in
sustaining Th1 responses at later stages in the presence of as yet
unidentified signals. Alternatively, the subclasses of DC may be
activated by different stimuli. Consistent with this notion, Schulz et
al. (21) have recently shown that
CD8- DC respond better to CpG DNA than to
extract of tachyzoites of T. gondii, while the converse is
true for CD8+ DC.
Our experiments with KO mice indicate that donor-derived IFN- and
IL-10 regulate in vivo the production of IL-12 by
CD8+ and CD8- DC,
respectively. It is unclear at present whether these cytokines are
produced by DC themselves or are present in the microenvironment where
DC differentiate. CD8+ DC have been shown to
produce IFN- upon IL-12 stimulation in vivo (22). A
recent report by Fukao et al. (23) demonstrates that, when
cultured with IL-12 alone, CD8+ DC produce
higher levels of IFN- than do CD8- DC.
Interestingly, the CD8- DC subset is capable
of producing high amounts of IFN- in the presence of IL-4 or IL-18
together with IL-12. The same authors have shown that mature DC
constitutively produce small amounts of IL-12, which induces the
secretion of IFN-, leading to up-regulation of IL-12 production
(23). It is therefore likely that
CD8+ DC produce IL-12 and IFN- in an
autocrine fashion, creating a positive feedback loop. This hypothesis
is supported by a report showing that splenic DC from
IFN--transgenic mice induced significantly higher levels of IL-12
compared with DC from control animals (24). Alternatively,
IFN- may directly promote the development of Th1 cells, although a
recent paper indicates that responsiveness of developing T lymphocytes
to IFN- disrupts their differentiation to Th1 effector cells
(25). Conversely, IL-10 appears to exert an inhibitory
effect on IL-12 production by CD8- DC.
Whether IL-10 is produced by CD8- DC or by
cells present in the vicinity during DC differentiation remains to be
determined. There is evidence that liver-derived DC progenitors
(26) and freshly isolated Peyer’s patch DC
(27) have the capacity to produce IL-10.
Our data further demonstrate that exogenous IFN- and IL-10 modulate
the function of DC subsets during their maturation in vitro. Incubation
of either subset with IFN- favors the priming of Th1 cells to the
detriment of Th2 cell development. In contrast, the presence of IL-10
during maturation leads to the development of DC with Th2-driving
function, as shown previously (5, 14, 28). Surprisingly,
IL-10 seems to selectively induce the apoptosis of
CD8+ DC, suggesting that IL-10 may favor Th2
priming by inducing death of IL-12-producing DC subset. Approximately
30% of CD8+ DC were apoptotic at the time
point tested, suggesting that additional mechanisms, such as impaired
migratory capacity and decreased costimulator function, may contribute
to the lack of Th1 priming. Of note, two reports indicate that IL-10
triggers apoptosis in human monocytes (29, 30).
The correlation between IL-12 production and the development of
polarized Th1 responses suggests that IL-12 may play a role in both Th1
and Th2 development (Fig. 5). Indeed,
CD8+ DC which do not produce IL-12 (i.e., from
IL-12-/- or IFN--/-
mice, or incubated in vitro with IL-10) fail to prime for Th1 but
instead induce the development of Th2-type cells. This observation
suggests that IL-12 may not only promote the development of Th1 cells
but may inhibit the development of Th2 cells. The Th2 "default"
pathway would therefore be spontaneously induced in the absence of
IL-12, a hypothesis that is still a matter of controversy.
Alternatively, activated Th1 cells may inhibit the development of Th2
cells, although kinetics studies suggest that the choice for Th
development is made very early, i.e., at the level of Ag presentation
(31). Our data clearly show that Th2 priming is
independent of DC-derived IL-4, an observation in contradiction with
two recent reports (3, 4). So far, evidence does not
indicate that transferred CD8- DC produce a
Th2-inducing cytokine, but rather indicates that they produce IL-10,
which inhibits IL-12 production.
|
Although the Th1-skewing capacity of CD8+ DC
appears strictly IL-12 dependent, incubation of either subset with
IFN- in vitro confers to CD8+ DC, and to a
lesser extent to CD8- DC, the capacity to
prime for Th1 that is partially independent of donor-derived IL-12.
Experiments are under way to test whether IL-12 produced by recipient
cells is involved. Alternatively, other cytokines may play a role in
Th1 priming by IFN--treated IL-12-deficient DC and include IL-18,
early T lymphocyte activation-1, etc. (36, 37).
Reports in the literature (for review, see Ref. 38) are
consistent with three models through which DC may control T cell
polarization: 1) subclasses of DC; 2) nature of the stimuli that
activate DC; and 3) kinetics of DC activation (39, 40).
The data presented herein emphasize the role of DC subsets and
activation signals on the T cell polarization process. We have not
directly tested the impact of the duration of DC activation, although
the level of IL-12 released by CD8+ DC
decreases after 18 h of in vitro maturation (our unpublished
observations), suggesting that at later time points these cells may
lose the capacity to prime Th1 cells.
The link between CD8+ and
CD8- DC subsets is still unclear.
CD8- DC are found in most lymphoid and
nonlymphoid organs, whereas CD8+ DC were
detected mainly in lymph nodes and spleen (41). Of note,
it has been shown recently that mouse Langerhans cells, negative for
CD8, acquire a CD8+ DC phenotype in vivo on
migration to the lymph nodes (42) and in vitro on CD40
ligation (43). Although these observations suggest that
CD8+ expression is acquired at some step of
maturation, we still believe that CD8+ and
CD8- DC located in the lymphoid organs
represent distinct populations. In favor of this notion, the phenotype
of splenic subsets appears stable upon in vitro maturation, and
injection of LPS results in maturation of both
CD8+ and CD8-
subclasses of DC and their redistribution into the T cell area (Ref.
44 and our unpublished observations).
In conclusion, our data indicate a dynamic regulation of the T cell
polarizing process of DC subsets. The function of
CD8+ and CD8- DC
appears flexible and is modulated by environmental factors, such as
IFN- and IL-10, which can be released by various cell types,
including cells of the innate system. Therefore, the Th-prone capacity
of DC migrating to the lymphoid organs is likely to transmit useful
information on the infected tissue to the T cells to induce the best
suitable immune response.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Muriel Moser, Département de Biologie Moléculaire, Université Libre de Bruxelles; rue des Prof. Jeener et Brachet, 12, 6041 Gosselies, Belgium. E-mail address: mmoser{at}dbm.ulb.ac.be
3 Abbreviations used in this paper: DC, dendritic cell; KLH, keyhole limpet hemocyanin; KO, knockout; WT, wild type.
Received for publication May 7, 2001. Accepted for publication August 21, 2001.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
/
-producing cells link innate and adaptive immunity. J. Exp. Med. 192:219.+ and CD8- subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J. Exp. Med. 189:587.+ and CD8- dendritic cells in the induction of primary immune responses in vivo. J. Leukocyte Biol. 66:242.[Abstract]
production and type-1 cytokine responses. Immunity 4:471.[Medline]
+ dendritic cells. Nat. Immun. 1:83.[Medline]
production by CD8+ lymphoid dendritic cells. J. Exp. Med. 189:1981. production by dendritic cells. J. Immunol. 164:64. transgenic mice: relevance to cancer development and therapeutic implications. Biochem. Biophys. Res. Commun. 259:294.[Medline]
signaling alters the function of T helper type 1 cells. J. Exp. Med. 192:977. production. Nature 378:88.[Medline]
and to bacterial IL-12 inducers: decreased ability of mature dendritic cells to produce IL-12 during the interaction with Th cells. J. Immunol. 162:3231.+ dendritic cells in vivo. Blood 96:1865.+ and CD8- subclasses of dendritic cells undergo a phenotypic and functional maturation in vitro and in vivo. J. Leukocyte Biol. 69:951.This article has been cited by other articles:
|
|
 |
|
  M. Motamedi, S. Arab, S. M. Moazzeni, M. Khamis Abadi, and J. Hadjati Improvement of a Dendritic Cell-Based Therapeutic Cancer Vaccine with Components of Toxoplasma gondii Clin. Vaccine Immunol., October 1, 2009; 16(10): 1393 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, M. Parker, C. Xia, R. Peng, C. Wasserfall, T. Clarke, L. Wu, T. Chowdhry, M. Campbell-Thompson, J. Williams, et al. Rabbit Polyclonal Mouse Antithymocyte Globulin Administration Alters Dendritic Cell Profile and Function in NOD Mice to Suppress Diabetogenic Responses J. Immunol., April 15, 2009; 182(8): 4608 - 4615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Ganesh, D. M. Cheatem, J. R. Sheng, C. Vasu, and B. S. Prabhakar GM-CSF-induced CD11c+CD8a--dendritic cells facilitate Foxp3+ and IL-10+ regulatory T cell expansion resulting in suppression of autoimmune thyroiditis Int. Immunol., March 1, 2009; 21(3): 269 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hemmi, J. Idoyaga, K. Suda, N. Suda, K. Kennedy, M. Noda, A. Aderem, and R. M. Steinman A New Triggering Receptor Expressed on Myeloid Cells (Trem) Family Member, Trem-Like 4, Binds to Dead Cells and Is a DNAX Activation Protein 12-Linked Marker for Subsets of Mouse Macrophages and Dendritic Cells J. Immunol., February 1, 2009; 182(3): 1278 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yamazaki, D. Dudziak, G. F. Heidkamp, C. Fiorese, A. J. Bonito, K. Inaba, M. C. Nussenzweig, and R. M. Steinman CD8+CD205+ Splenic Dendritic Cells Are Specialized to Induce Foxp3+ Regulatory T Cells J. Immunol., November 15, 2008; 181(10): 6923 - 6933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Joyee, H. Qiu, Y. Fan, S. Wang, and X. Yang Natural Killer T Cells Are Critical for Dendritic Cells to Induce Immunity in Chlamydial Pneumonia Am. J. Respir. Crit. Care Med., October 1, 2008; 178(7): 745 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Maroof and P. M. Kaye Temporal Regulation of Interleukin-12p70 (IL-12p70) and IL-12-Related Cytokines in Splenic Dendritic Cell Subsets during Leishmania donovani Infection Infect. Immun., January 1, 2008; 76(1): 239 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 H. S. Bandukwala, B. S. Clay, J. Tong, P. D. Mody, J. L. Cannon, R. A. Shilling, J. S. Verbeek, J. V. Weinstock, J. Solway, and A. I. Sperling Signaling through Fc{gamma}RIII is required for optimal T helper type (Th)2 responses and Th2-mediated airway inflammation J. Exp. Med., August 6, 2007; 204(8): 1875 - 1889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Johnson and P. Scott STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity to Leishmania major J. Immunol., June 1, 2007; 178(11): 7259 - 7266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Jirmanova, D. Jankovic, A. J. Fornace Jr., and J. D. Ashwell Gadd45{alpha} Regulates p38-Dependent Dendritic Cell Cytokine Production and Th1 Differentiation J. Immunol., April 1, 2007; 178(7): 4153 - 4158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Stober, U. G. Lange, M. T. M. Roberts, A. Alcami, and J. M. Blackwell Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory against Leishmania major in Susceptible BALB/c Mice Infect. Immun., February 1, 2007; 75(2): 852 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Obayashi, T. Doi, and S. Koyasu Dendritic cells suppress IgE production in B cells Int. Immunol., February 1, 2007; 19(2): 217 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Boonstra, R. Rajsbaum, M. Holman, R. Marques, C. Asselin-Paturel, J. P. Pereira, E. E. M. Bates, S. Akira, P. Vieira, Y.-J. Liu, et al. Macrophages and Myeloid Dendritic Cells, but Not Plasmacytoid Dendritic Cells, Produce IL-10 in Response to MyD88- and TRIF-Dependent TLR Signals, and TLR-Independent Signals J. Immunol., December 1, 2006; 177(11): 7551 - 7558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ejrnaes, C. M. Filippi, M. M. Martinic, E. M. Ling, L. M. Togher, S. Crotty, and M. G. von Herrath Resolution of a chronic viral infection after interleukin-10 receptor blockade J. Exp. Med., October 30, 2006; 203(11): 2461 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Sheng, L. Li, B. B. Ganesh, C. Vasu, B. S. Prabhakar, and M. N. Meriggioli Suppression of Experimental Autoimmune Myasthenia Gravis by Granulocyte-Macrophage Colony-Stimulating Factor Is Associated with an Expansion of FoxP3+ Regulatory T Cells J. Immunol., October 15, 2006; 177(8): 5296 - 5306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wen, C. M. Hogaboam, J. Gauldie, and S. L. Kunkel Severe Sepsis Exacerbates Cell-Mediated Immunity in the Lung Due to an Altered Dendritic Cell Cytokine Profile Am. J. Pathol., June 1, 2006; 168(6): 1940 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, J. Arp, X. Huang, W. Liu, S. Ramcharran, J. Jiang, B. Garcia, N. Kanai, W. Min, P. J. O'Connell, et al. Distinct Subsets of Dendritic Cells Regulate the Pattern of Acute Xenograft Rejection and Susceptibility to Cyclosporine Therapy J. Immunol., March 15, 2006; 176(6): 3525 - 3535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 D. A. Hokey, A. T. Larregina, G. Erdos, S. C. Watkins, and L. D. Falo Jr. Tumor Cell Loaded Type-1 Polarized Dendritic Cells Induce Th1-Mediated Tumor Immunity Cancer Res., November 1, 2005; 65(21): 10059 - 10067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. K. Teixeira, B. P. F. Fonseca, A. Vieira-de-Abreu, B. A. Barboza, B. K. Robbs, P. T. Bozza, and J. P. B. Viola IFN-{gamma} Production by CD8+ T Cells Depends on NFAT1 Transcription Factor and Regulates Th Differentiation J. Immunol., November 1, 2005; 175(9): 5931 - 5939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cohen-Sfady, G. Nussbaum, M. Pevsner-Fischer, F. Mor, P. Carmi, A. Zanin-Zhorov, O. Lider, and I. R. Cohen Heat Shock Protein 60 Activates B Cells via the TLR4-MyD88 Pathway J. Immunol., September 15, 2005; 175(6): 3594 - 3602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, H. Huang, J. Yuan, D. Sun, W.-S. Hou, J. Gordon, and J. Xiang CD4-8- Dendritic Cells Prime CD4+ T Regulatory 1 Cells to Suppress Antitumor Immunity J. Immunol., September 1, 2005; 175(5): 2931 - 2937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, X. Bi, S. Xu, and J. Xiang Tumor-Infiltrating Dendritic Cell Subsets of Progressive or Regressive Tumors Induce Suppressive or Protective Immune Responses Cancer Res., June 1, 2005; 65(11): 4955 - 4962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Filatenkov, E. L. Jacovetty, U. B. Fischer, J. M. Curtsinger, M. F. Mescher, and E. Ingulli CD4 T Cell-Dependent Conditioning of Dendritic Cells to Produce IL-12 Results in CD8-Mediated Graft Rejection and Avoidance of Tolerance J. Immunol., June 1, 2005; 174(11): 6909 - 6917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gangi, C. Vasu, D. Cheatem, and B. S. Prabhakar IL-10-Producing CD4+CD25+ Regulatory T Cells Play a Critical Role in Granulocyte-Macrophage Colony-Stimulating Factor-Induced Suppression of Experimental Autoimmune Thyroiditis J. Immunol., June 1, 2005; 174(11): 7006 - 7013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hanada, K. Tanaka, Y. Matsumura, M. Yamauchi, H. Nishinakamura, H. Aburatani, R. Mashima, M. Kubo, T. Kobayashi, and A. Yoshimura Induction of Hyper Th1 Cell-Type Immune Responses by Dendritic Cells Lacking the Suppressor of Cytokine Signaling-1 Gene J. Immunol., April 1, 2005; 174(7): 4325 - 4332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tamura, P. Tailor, K. Yamaoka, H. J. Kong, H. Tsujimura, J. J. O'Shea, H. Singh, and K. Ozato IFN Regulatory Factor-4 and -8 Govern Dendritic Cell Subset Development and Their Functional Diversity J. Immunol., March 1, 2005; 174(5): 2573 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Zhang, X. Ding, and R. A. Daynes The Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type I by Lymphocytes Provides a Novel Means for Intracrine Regulation of Glucocorticoid Activities J. Immunol., January 15, 2005; 174(2): 879 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rivas-Carvalho, M. A. Meraz-Rios, L. Santos-Argumedo, S. Bajana, G. Soldevila, M. E. Moreno-Garcia, and C. Sanchez-Torres CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines Int. Immunol., September 1, 2004; 16(9): 1251 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yang, F. M. Murillo, K.-Y. Lin, W. H. Yutzy IV, S. Uematsu, K. Takeda, S. Akira, R. P. Viscidi, and R. B. S. Roden Human Papillomavirus Type-16 Virus-Like Particles Activate Complementary Defense Responses in Key Dendritic Cell Subpopulations J. Immunol., August 15, 2004; 173(4): 2624 - 2631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Marino, S. Pawar, C. L. Fuller, T. A. Reinhart, J. L. Flynn, and D. E. Kirschner Dendritic Cell Trafficking and Antigen Presentation in the Human Immune Response to Mycobacterium tuberculosis J. Immunol., July 1, 2004; 173(1): 494 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Elsen, J. Doussiere, C. L. Villiers, M. Faure, R. Berthier, A. Papaioannou, N. Grandvaux, P. N. Marche, and P. V. Vignais Cryptic O2--generating NADPH oxidase in dendritic cells J. Cell Sci., May 1, 2004; 117(11): 2215 - 2226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Lavelle, A. Jarnicki, E. McNeela, M. E. Armstrong, S. C. Higgins, O. Leavy, and K. H. G. Mills Effects of cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent J. Leukoc. Biol., May 1, 2004; 75(5): 756 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bjorck Dendritic Cells Exposed to Herpes Simplex Virus In Vivo Do Not Produce IFN-{alpha} after Rechallenge with Virus In Vitro and Exhibit Decreased T Cell Alloreactivity J. Immunol., May 1, 2004; 172(9): 5396 - 5404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yasumi, K. Katamura, T. Yoshioka, T.-a. Meguro, R. Nishikomori, T. Heike, M. Inobe, S. Kon, T. Uede, and T. Nakahata Differential Requirement for the CD40-CD154 Costimulatory Pathway during Th Cell Priming by CD8{alpha}+ and CD8{alpha}− Murine Dendritic Cell Subsets J. Immunol., April 15, 2004; 172(8): 4826 - 4833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Blois, C. D. Alba Soto, M. Tometten, B. F. Klapp, R. A. Margni, and P. C. Arck Lineage, Maturity, and Phenotype of Uterine Murine Dendritic Cells Throughout Gestation Indicate a Protective Role in Maintaining Pregnancy Biol Reprod, April 1, 2004; 70(4): 1018 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Johansson and M. J. Wick Liver Dendritic Cells Present Bacterial Antigens and Produce Cytokines upon Salmonella Encounter J. Immunol., February 15, 2004; 172(4): 2496 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. De Trez, M. Brait, O. Leo, T. Aebischer, F. A. Torrentera, Y. Carlier, and E. Muraille Myd88-Dependent In Vivo Maturation of Splenic Dendritic Cells Induced by Leishmania donovani and Other Leishmania Species Infect. Immun., February 1, 2004; 72(2): 824 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Attanavanich and J. F. Kearney Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells J. Immunol., January 15, 2004; 172(2): 803 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kuipers, D. Hijdra, V. C. de Vries, H. Hammad, J.-B. Prins, A. J. Coyle, H. C. Hoogsteden, and B. N. Lambrecht Lipopolysaccharide-Induced Suppression of Airway Th2 Responses Does Not Require IL-12 Production by Dendritic Cells J. Immunol., October 1, 2003; 171(7): 3645 - 3654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Doxsee, T. R. Riter, M. J. Reiter, S. J. Gibson, J. P. Vasilakos, and R. M. Kedl The Immune Response Modifier and Toll-Like Receptor 7 Agonist S-27609 Selectively Induces IL-12 and TNF-{alpha} Production in CD11c+CD11b+CD8- Dendritic Cells J. Immunol., August 1, 2003; 171(3): 1156 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Oldenhove, M. de Heusch, G. Urbain-Vansanten, J. Urbain, C. Maliszewski, O. Leo, and M. Moser CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo J. Exp. Med., July 21, 2003; 198(2): 259 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Edwards, D. Chaussabel, S. Tomlinson, O. Schulz, A. Sher, and C. Reis e Sousa Relationships Among Murine CD11chigh Dendritic Cell Subsets as Revealed by Baseline Gene Expression Patterns J. Immunol., July 1, 2003; 171(1): 47 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lugo-Villarino, R. Maldonado-Lopez, R. Possemato, C. Penaranda, and L. H. Glimcher T-bet is required for optimal production of IFN-{gamma} and antigen-specific T cell activation by dendritic cells PNAS, June 24, 2003; 100(13): 7749 - 7754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vasu, R.-N. E. Dogan, M. J. Holterman, and B. S. Prabhakar Selective Induction of Dendritic Cells Using Granulocyte Macrophage-Colony Stimulating Factor, But Not fms-Like Tyrosine Kinase Receptor 3-Ligand, Activates Thyroglobulin-Specific CD4+/CD25+ T Cells and Suppresses Experimental Autoimmune Thyroiditis J. Immunol., June 1, 2003; 170(11): 5511 - 5522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-N. E. Dogan, C. Vasu, M. J. Holterman, and B. S. Prabhakar Absence of IL-4, and Not Suppression of the Th2 Response, Prevents Development of Experimental Autoimmune Graves' Disease J. Immunol., February 15, 2003; 170(4): 2195 - 2204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Straw, A. S. MacDonald, E. Y. Denkers, and E. J. Pearce CD154 Plays a Central Role in Regulating Dendritic Cell Activation During Infections That Induce Th1 or Th2 Responses J. Immunol., January 15, 2003; 170(2): 727 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Boonstra, C. Asselin-Paturel, M. Gilliet, C. Crain, G. Trinchieri, Y.-J. Liu, and A. O'Garra Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development: Dependency on Antigen Dose and Differential Toll-like Receptor Ligation J. Exp. Med., January 6, 2003; 197(1): 101 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. R. Lankford and D. M. Frucht A unique role for IL-23 in promoting cellular immunity J. Leukoc. Biol., January 1, 2003; 73(1): 49 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schiavoni, F. Mattei, P. Sestili, P. Borghi, M. Venditti, H. C. Morse III, F. Belardelli, and L. Gabriele ICSBP Is Essential for the Development of Mouse Type I Interferon-producing Cells and for the Generation and Activation of CD8{alpha}+ Dendritic Cells J. Exp. Med., December 2, 2002; 196(11): 1415 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Ritz, M. J. Cundall, B. U. Gajewska, D. Alvarez, J.-C. Gutierrez-Ramos, A. J. Coyle, A. N. J. McKenzie, M. R. Stampfli, and M. Jordana Granulocyte Macrophage Colony-Stimulating Factor-Driven Respiratory Mucosal Sensitization Induces Th2 Differentiation and Function Independently of Interleukin-4 Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 428 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Edwards, S. P. Manickasingham, R. Sporri, S. S. Diebold, O. Schulz, A. Sher, T. Kaisho, S. Akira, and C. Reis e Sousa Microbial Recognition Via Toll-Like Receptor-Dependent and -Independent Pathways Determines the Cytokine Response of Murine Dendritic Cell Subsets to CD40 Triggering J. Immunol., October 1, 2002; 169(7): 3652 - 3660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Legge, R. K. Gregg, R. Maldonado-Lopez, L. Li, J. C. Caprio, M. Moser, and H. Zaghouani On the Role of Dendritic Cells in Peripheral T Cell Tolerance and Modulation of Autoimmunity J. Exp. Med., July 15, 2002; 196(2): 217 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Yrlid and M. J. Wick Antigen Presentation Capacity and Cytokine Production by Murine Splenic Dendritic Cell Subsets upon Salmonella Encounter J. Immunol., July 1, 2002; 169(1): 108 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Muraille, C. De Trez, B. Pajak, M. Brait, J. Urbain, and O. Leo T Cell-Dependent Maturation of Dendritic Cells in Response to Bacterial Superantigens J. Immunol., May 1, 2002; 168(9): 4352 - 4360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shaw, V. Grund, L. Durling, D. Crane, and H. D. Caldwell Dendritic Cells Pulsed with a Recombinant Chlamydial Major Outer Membrane Protein Antigen Elicit a CD4+ Type 2 Rather than Type 1 Immune Response That Is Not Protective Infect. Immun., March 1, 2002; 70(3): 1097 - 1105. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
