BIOLOGY OF REPRODUCTION 70, 1018–1023 (2004)
Published online before print 17 December 2003.
Lineage, Maturity, and Phenotype of Uterine Murine Dendritic Cells Throughout
Gestation Indicate a Protective Role in Maintaining Pregnancy1
Sandra M. Blois,3,4Catalina D. Alba Soto,5Mareike Tometten,3Burghard F. Klapp,3Ricardo A. Margni,4
and Petra C. Arck2,3
Charite ´,3Department of Internal Medicine, Biomedizinisches Forschungszentrum, Campus Virchow, Humboldt
University of Berlin, 13353 Berlin, Germany
IDEHU—Humoral Immunity Studies Institute-National Council of Scientific and Technological Research (CONICET),4
University of Buenos Aires, 1113 Buenos Aires, Argentina
Department of Microbiology,5Parasitology, and Immunology, School of Medicine, University of Buenos Aires, Argentina
Dendritic cells (DCs) are known to play a major role in the
induction, maintenance, and regulation of immune responses.
Recently, DCs have been described to be present at the feto-
maternal interface in human decidua. However, only limited in-
formation is available about DC presence, phenotype, and—
more importantly—function throughout gestation. Thus, we an-
alyzed local (uterine) and systemic (blood) DCs in a murine
model. DBA/2J mated CBA/J females with vaginal plugs were
separated and killed on Gestation Days (GDs) 1.5, 3.5, 5.5, 6.5,
7.5, 8.5, 10.5, 13.5, 15.5, or 17.5. Frequency of uterine and
blood CD11c?DC, phenotype (coexpression of CD8? and ma-
jor histocompatibility complex class II [MHC II] antigens), and
presence of intracellular cytokines (interleukins 12 and 10) were
determined by flow cytometry. The morphology of DC in the
pregnant uterus was evaluated by immunohistochemistry. In
uterus, the relative number of CD11c?cells increased from GD
5.5, reaching a plateau on GD 9.5 until GD 17.5, while a tran-
sient peak of systemic CD11c?cells was found on GD 8.5 and
10.5. The vast majority of uterine DCs were CD8??and thus,
belonged to the myeloid lineage. Interestingly, a significant peak
of lymphoid DC was present on GD 1.5 and 5.5. Further, sig-
nificantly more intracellular interleukin 10 than interleukin 12
was present in CD11c?cells. Interestingly, mature DCs (MHC
II?) were diminished from GD 5.5 to 8.5. Characterization of
CD11c?cell kinetics in uterus and blood reveals variation of
phenotype during pregnancy, pointing toward an eminent im-
munoregulatory role of DCs throughout gestation at the feto-
cytokines, decidua, immunology, implantation, pregnancy
Dendritic cells (DCs) are critical immune sentinels,
which are uniquely designed to initiate and coordinate in-
nate and adaptive immune responses . DCs are not only
essential for the induction of primary immune responses
1Supported by grants from the Charite ´ to P.C.A. and by a scholarship from
the German Academic Student Exchange (DAAD) to S.M.B.
2Correspondence: Petra Clara Arck, Biomedizinisches Forschungszen-
trum, Raum 2.0549, Augustenburger Platz 1, 13353 Berlin, Germany.
FAX: ?49 30 450 553962; e-mail: email@example.com
Received: 28 August 2003.
First decision: 3 October 2003.
Accepted: 3 December 2003.
? 2004 by the Society for the Study of Reproduction, Inc.
ISSN: 0006-3363. http://www.biolreprod.org
but may also be important for the induction of immunolog-
ical tolerance as well as for the regulation of some type of
T-cell-mediated immune responses . Recent findings de-
scribe how immature DCs may contribute to the induction
of tolerance, whereas mature DCs can influence the gen-
eration of proinflammatory responses [3, 4]. In addition, it
has been proposed that the different DC subsets may play
a prominent role in dictating the quantity and quality of
immune responses .
In mice, DCs can be classified on the basis of their
CD8? expression, whereby CD8??- and CD8??-DCs have
been considered as myeloid and lymphoid, respectively .
However, it has been reported that both subpopulations can
be generated from unique lymphoid committed precursor
populations . The CD8??lymphoid DC subset is con-
sidered to prime naive CD4?T cells to synthesize Th1 cy-
tokines, such as interleukin (IL)-12, whereas the CD8??
myeloid DC subset is thought to prime naive CD4?T cells
to produce Th2 cytokines, e.g., IL-10 [5, 8].
In pregnancy maintenance, several mechanisms are in-
volved in the maternal tolerance against the fetus. Half a
century ago, Medawar considered three mechanisms, which
are still valid to date: 1) anatomic separation of fetus and
mother, 2) antigenic immaturity of the fetus, and 3) im-
munologic tolerance of the mother . The maternal bal-
ance between active immunity and tolerance at the feto-
maternal interface, which is the site of contact between
mother and child, is of crucial importance. Studies from
Heikkinen et al. suggest that immunologic tolerance of the
mother might be explained by the immunoinhibitory func-
tion of decidual macrophages at the feto-maternal interface
However, because DCs constitute a complex system of
cells uniquely able to commit between tolerogenic and im-
munogenic responses, they represent one major aspect to
understand maternal tolerance. In fact, there is evidence
that DCs could play a protective and immunoregulatory
role at the feto-maternal interface. Ka ¨mmerer et al. de-
scribed the presence of immunostimulatory mature DCs in
decidual tissue during the early phase of human pregnancy.
DCs seem to participate in the induction of decidual tol-
erance of the conceptus . More recently, two pregnan-
cy-protective molecules associated with DCs, CD200 and
indoleamine 2,3-dioxygenase, have been suggested to play
an immunoregulatory role at the maternal interface [12,
Taking into account all this evidence, we hypothesized
DENDRITIC CELLS DURING MURINE PREGNANCY
that DCs possess a regulatory function at the feto-maternal
interface. Moreover, these cells might provide the signals
deciding between allograft rejection and tolerance during
gestation. Therefore, the aims of this study were
1. to evaluate the presence of the CD11c?(murine DC
marker) in uterine and blood cells during pregnancy in
CBA/J ? DBA/2J murine model,
2. to characterize the lineage of CD11c?DC present at the
feto-maternal interface and in blood, CD8??for lym-
phoid, and CD8??for myeloid, respectively. Further-
more, to evaluate the presence of major histocompati-
bility complex (MHC) II as a marker for DC maturity,
3. to analyze the phenotype of DC cytokine production
during gestation, in particular the production of IL-10
MATERIALS AND METHODS
Mice were purchased from Charles River (Sulzfeld, Germany) and
maintained in an animal facility with a 12L:12D cycle. Animal care and
experimental procedures were followed according to institutional guide-
lines and conformed to requirements of the state authority for animal re-
search conduct (LaGetSi, Berlin). After overnight cohabitation of CBA/J
females with DBA/2J males, females with vaginal plugs, which equals
Day 0.5, were separated from the males and assigned to different groups
and killed on Gestation Days (GDs) 1.5, 3.5, 5.5, 6.5, 7.5, 8.5, 10.5, 13.5,
15.5, or 17.5 (n ? 7 in each GD). Also, we analyzed nonpregnant mice
(n ? 5). Random selection of these nonpregnant mice allowed us not to
distinguish between stages of the estrous cycle of these mice, and thus,
the data shown represent those for a pool of cells from animals either in
estrus or not. Uteri were removed and divided into pieces, one section
was frozen for immunochemistry, and resident uterine cells were isolated
as described below.
Blood samples were obtained by retro-orbital puncture shortly before
the mice were killed. Blood was collected in heparinized tubes. After
treatment with ammonium chloride lysis buffer for 10 min to deplete
erythrocytes, the cells were washed twice with sterile phosphate-buffered
Uterus Cell Isolation
After the mice were killed, the abdomen was carefully opened and
access to the uterus was gained by pushing intestinal tissue to the side.
The uterus was then removed by surgical cuts at the cervix and the ovaries.
Then the uteri were fixed to a clamp at the cervix, which gave enough
stability and allowed carefully cutting along the uterine horns. Then the
embryos and placentas were cautiously peeled from the decidua. The re-
maining parts of the uterus, consisting of deciduas and myometrium, were
washed in PBS to remove possible blood contamination. Then uterus-
resident cells were isolated by a method described by Ka ¨mmerer et al.
, with some modifications. In brief, the uterus was again washed with
sterile PBS, carefully cut into small pieces, collected in tubes containing
Hanks balanced salt solution (HBSS), and digested for 20 min at 37?C
under slight agitation in HBSS with 200 U/ml hyaluronidase, 1 mg/ml
collagenase type IV, 0.2 mg/ml DNase I, and 1 mg/ml bovine serum al-
bumin/fraction V. All reagents were purchased from Sigma (Taufkirchen,
Germany). Thereafter, the isolated cells were collected in a fresh tube
through a 100-?m net (BD Biosciences, San Jose, CA) and washed with
RPMI (developed at the Roswell Park Memorial Institute [Buffalo, New
York], hence the acronym is RPMI; purchased at Gibco, Invitrogen, Eg-
genstein, Germany)-10% fetal bovine serum (FBS). The procedure was
repeated twice, with HBSS medium containing no cocktail of enzymes.
Cell populations were obtained by density-gradient centrifugation in a
1.088 g/ml Lympholyte-M solution (Cedarlane Labs, Hornby, ON, Cana-
da) upon centrifugation at 2400 rpm for 20 min at room temperature (RT).
The low-density fraction at the interface between Lympholyte-M and me-
dium was collected and washed several times. We then counted the total
number of uterine cells and observed some variations between the different
days of gestation; however, significant differences of isolated cells per
milliliter of cell suspension between the various days of gestation could
not be detected.
Flow Cytometric Analysis
For flow cytometry, the uterine and blood cells were incubated for 3
h with Brefeldin A (106cells/ml medium with 1 ?l/ml of Golgi Plug; BD
Pharmingen, Heidelberg, Germany) in RPMI with FBS in a humidified
incubator at 37?C with 5% CO2. Brefeldin A is a commonly used agent
that blocks cytokine secretion through inhibition of the Golgi apparatus.
Flow cytometry was performed as follows: for immunostaining, uterus
cells were washed twice with ice-cold PBS supplemented with 1% bovine
serum albumin (Sigma) and 0.1% Natrium Azid (Sigma). Two percent of
normal mouse serum was added to avoid nonspecific binding by Fc re-
ceptors. Cells were then incubated 30 min at 4?C with previously opti-
mized amounts of one or more of the following conjugated murine mono-
clonal antibodies (Mabs): anti-CD8a fluorescein isothyocianate, anti-Ie-K
(MHC II)-PE, and the biotinylated Mab anti-CD11c. All Mabs were pur-
chased from BD Biosciences. Streptavidin-PerCP was used as a second-
step reagent. Cells were washed, fixed using Fix solution (Becton Dick-
inson, Erembodegem, Belgium), and incubated for 20 min at RT in the
dark. Subsequently, the cells were washed and permeabilized, using fluo-
rescence activated cell sorting (FACS) permeabilizing solution (Becton
Dickinson), followed by incubation with intracellular antibody PE-labeled
IL-12 and IL-10 for 30 min at 4?C in the dark. As controls, cells were
stained with the corresponding isotype-matched Mab. The cells were then
washed and analyzed. The acquisition was performed using a FACS Cal-
ibur (Becton Dickinson). A minimum of 30000 events per analysis were
examined. Instrument compensation was set in each experiment by single-
color stained samples. Data were analyzed by Cell Quest software. Flow
cytometry results were expressed as percentage of cells positive for the
surface marker and for intracellular cytokines.
Immunohistochemical Staining for CD11c?
Eight-micron cryosections were incubated with avidin- and biotin-
blocking solution (Vector Laboratories, Burlingame, CA), followed by an-
other blockade step using protein blocking agent (Immunotech, Beckman
Coulter, Krefeld, Germany). The biotinylated hamster-anti-mouse CD11c
Mab (BD Biosciences) was diluted 1:100 in Tris-buffered saline (TBS)
containing 1% FBS and applied for 1 h. As the amplification and devel-
oping system, we used avidin-biotin-alkaline phosphate complex (Vector
Laboratories) 1:100 in TBS for 30 min. After washing, a routine staining
procedure for alkaline phosphate was used and sections were counter-
stained with Mayer hematoxylin. Thereafter, sections were covered with
Kaiser glycerol gelatin. Slides were examined using a Zeiss Axioscope
light microscope (Carl Zeiss Inc., Oberkochen, Germany). Photo docu-
mentation was performed using a digital image analysis system (Zeiss
Statistical significance was determined using the nonparametric Mann-
Whitney U-test for comparison of two samples. The observations over
time were tested with the Kruskal-Wallis test. The results are presented as
mean and SD. Differences at P ? 0.05 are considered statistically signif-
Differential Expression of CD11c in Uterus and Blood
Because murine DC subsets can be identified by their
expression of CD11c on the cell surface , we first fo-
cused on the expression of this distinct DC cell surface
molecule on uterus and blood cells. The percentages of
CD11c?cells at the uterus and in the blood of nonpregnant
mice were not different from those of pregnant mice on GD
1.5 (Fig. 1). CD11c expression in uterine cells significantly
increased on completion of implantation (GD 5.5), reaching
a plateau of relative CD11c?cell numbers of 10% among
the resident uterine cells. In general, the percentage of cells
expressing CD11c was lower in blood than in the uterus
BLOIS ET AL.
ing gestation (Gestation Day [GD] 1.5–17.5) in the CBA ? DBA mouse
model. NP means uterus from mice that were not mated. Levels of sig-
nificance, obtained by the Kruskal-Wallis test, were reached for GD 5.5
(indicated by a fat line), compared with GDs 1.5 and 3.5 (*, P ?0.05)
and for GD 8.5 (again pointed out by the fat line), when compared with
GD 1.5, 3.5, 5.5, 6.5, 10.5, 13.5, 15.5, and 17.5, respectively. *, a sig-
nificant increase with P ? 0.05; **, with P ? 0.01; and ***, with P ?
0.001. Data have purposely been depicted as means rather than medians
because presentation of these nonparametric data as box plots depicting
the median with 25th and 75th percentiles would lack easy orientation
and clarity, especially in the following figures.
Mean percentage of CD11c?cells isolated from the uterus dur-
nant CBA mice on different days of gestation. NP means uterus from mice
that were not mated. The bars indicate the percentage of positivity and
negativity for CD8?. *, P ? 0.05; significant differences were present on
GDs 1.5 and 5.5 compared with all other GDs investigated.
Analysis of CD8? coexpression on CD11c?uterus cells of preg-
TABLE 1. The relative number of CD11c?cells in blood throughoutpreg-
nancy in the CBA/J ? DBA/2J mouse model.
0.29 ? 0.08
0.37 ? 0.03
0.72 ? 0.09
0.63 ? 0.10
0.67 ? 0.05
1.99 ? 0.37a
1.50 ? 0.27b
0.53 ? 0.06
0.36 ? 0.04
0.66 ? 0.05
11 ? 1
14 ? 1
24 ? 4
13 ? 2
14 ? 7
9 ? 2
65 ? 7c
53 ? 13d
29 ? 2
19 ? 5
7 ? 1
42 ? 7
19 ? 5
27 ? 6
23 ? 8
14 ? 2
44 ? 5
58 ? 13
85 ? 5e
87 ? 3e
a,b aP ? 0.001;bP ? 0.01, CD11c?cells between GD 8.5, 10.5, and the
rest of the GDs.
c,d cP ? 0.001;dP ? 0.01, CD8??/CD11c?cells between GD 10.5, 13.5,
and other GDs.
eP ? 0.05, MHC II?/CD11c?cells between GD 15.5, 17.5, and the rest
of the GDs.
pregnancy. NP means uterus from mice that were not mated. *, P ? 0.05;
**, P ? 0.01; significant decrease of MHC II?/CD11?population was
present from GD 5.5 to GD 8.5 compared with all other GDs tested.
Analysis of MHC II coexpression in CD11c?uterine cells during
during pregnancy (see Fig. 1 and Table 1). In blood, we
found an increase of CD11c expression on GD 8.5 and 10.5
compared with the other evaluated GDs (see Table 1).
Lymphoid/Myeloid Lineage of CD11c?Cells in Uterus
Next, we determined, again by flow cytometry, the ex-
pression of CD8? in uterine and blood CD11c?cells. In
the uterus, the vast majority of CD11c?cells are CD8??;
thus, they pertain to the myeloid lineage. Nevertheless, a
significant and transient shift toward a lymphoid phenotype
of uterine DCs could be detected on GDs 1.5 and 5.5 (Fig.
Also in the blood, the percentage of myeloid CD11c?
cells, as identified by CD8? negativity, was predominant.
The highest levels of lymphoid CD11c?were observed on
GDs 10.5 and 13.5 (see Table 1), which were significantly
different compared with the other investigated GDs.
Expression of MHC Class II Molecules by CD11c?Cells
Further, we investigated whether CD11c?cells coex-
pressed MHC class II molecules during gestation, which
may then be considered as mature DCs. Indeed, we found
that CD11c?from blood and uterine cells spontaneously
express MHC class II throughout pregnancy (see Fig. 3 and
Table 1). In the uterus, less than 30% of resident CD11c?
cells expressed MHC class II molecules; thus, the majority
of uterine DCs are immature. Surprisingly, from GD 5.5 to
GD 8.5, the expression of MHC class II molecules on the
surface of uterine CD11c?cells was significantly reduced.
A high percentage of MHC class II expressing CD11c?
cells in blood could be detected late in gestation (GDs 15.5
Cytokine Expression in CD11c?Cells
Orientation of immune responses by DCs is directly re-
lated to their profile of cytokines. Therefore, we studied the
expression of IL-12 as a Th1 marker/inducer and IL-10 as
a Th2 marker in uterine and blood CD11c?cells during
pregnancy (Fig. 4 and Table 2).
The relative number of IL-12-producing CD11c?cells
DENDRITIC CELLS DURING MURINE PREGNANCY
in CD11c?uterus cells during gestation and in mice that were not mated
(NP). *, P ? 0.05; **, P ? 0.01; ***, P ? 0.001.
Intracellular presence of IL-10 (gray bars) and IL-12 (black bars)
TABLE 2. Cytokine expression in CD11c?blood cells during pregnancy.
16 ? 5
24 ? 4
49 ? 9a
13 ? 3
10 ? 3
22 ? 2
26 ? 3a
37 ? 7a
34 ? 1
33 ? 2
10 ? 1
10 ? 2
25 ? 4
6 ? 3
6 ? 4
4 ? 1
8 ? 3
12 ? 3
24 ? 4
28 ? 3
aP ? 0.05, comparing IL-10 and IL-12 expressing CD11c?cells on GD
5.5, 10.5, and 13.5
CD11c?cells in deciduas (dec) (A and B)
and placenta (pl)/interface (C and D) on
GD 8.5. CD11c?cells appear with red
staining. Scale bar ? 20 ?m.
Localization and shape of
in uterus was constantly lower than in the blood. In the
uterus, the intracellular presence of IL-10 was significantly
higher than the expression of IL-12 in CD11c?cells, with
the exception of GD 5.5.
In the blood, IL-10-producing DCs predominate mildly
over IL-12-producing DCs. However, on GDs 5.5, 10.5, and
13.5, the domination of IL-10 over IL-12 increased signif-
Tissue Distribution of CD11c Expression During
To further characterize CD11c?DC cells, we performed
immunohistochemical staining on frozen uterus tissue sec-
tions (Fig. 5). CD11c?-expressing cells were of ovoid and
macrophage shape. These positive cells could be detected
in uterine as well as in placental tissue. Interestingly, they
did not differ morphologically from each other.
The presence of DC in the maternal decidua points at a
crucial biological role at the feto-maternal interface. The
uterus is generally considered to be an immunologically
privileged site for the implanted semiallogeneic embryo with
respect to the aggressive maternal immune response .
From the data presented here, some insights on the precise
function of DCs in pregnancy maintenance have been
gained, motivating us to discuss the following points:
1. What may be the possible role for the observed increase
of CD11c?uterus cells between GDs 5.5 and 17.5?
2. What may be the explanation for the predominance of
the myeloid (CD8??) over lymphoid (CD8??) pheno-
BLOIS ET AL.
type of uterine DCs and why do DCs express higher
levels of Th2 (IL-10) than Th1 (IL-12) cytokines?
3. What may cause the downregulation of MHC class II
molecules on GDs 5.5 to 8.5?
4. What may be the explication for the differences of fre-
quency and phenotype between uterine and blood DCs?
In the present study, we observed that the relative num-
ber of CD11c?uterine cells is not constant during preg-
nancy. Indeed, we found an increase of CD11c?uterus cells
from GD 5.5, with the highest point of expression on GD
8.5, reaching a plateau on GD 9.5 until GD 17.5. The in-
crement of CD11c?uterine cells occurs simultaneously
with the decisive phase of gestation, when implantation
takes place. In fact, Gorczynski et al.  recently de-
scribed that CD200, a further molecule expressed on DCs,
is associated with the maintenance of pregnancy in allo-
geneic mouse models, such as the CBA/J ? BALB/c model
 and the CBA/J ? DBA/2J model, which has been re-
ferred to as abortion prone because an increased abortion
rate can be induced by application of lipopolysaccharide,
Th1 cytokines, or stress exposure [12, 15]. Taking this into
account, we suggest that DCs are involved in the immu-
nological events that accompany the maintenance of mam-
malian pregnancy at the time of implantation, which points
toward understanding discussion aspect 1.
The different murine DC subtypes share a common ca-
pacity to present antigens to T cells and promote cell-cycle
progression. However, they differ in some aspects of DC-
T-cell signaling that determine the type of immune re-
sponse. Thus, CD8?DCs have the ability to induce a Th1-
biased cytokine response, whereas CD8?DCs are prone to
induce a Th2-biased response [16–18].
Cytokines are known to regulate the rejection or main-
tenance of pregnancy. Th1 cytokines (IL-2, tumor necrosis
factor ?, IL-12, interferon ?) have been shown to boost the
abortion rate, while Th2 cytokines (IL-3, IL-4, IL-10) ap-
pear to be pregnancy-protective [19–21]. The balance be-
tween Th1 and Th2 is crucial for successful pregnancy,
whereby the temporal positioning of Th1-type and Th2-
type cytokines and their relative concentrations appear to
be quite critical. It is generally accepted that some Th1-
type cytokines are involved in mediating the communica-
tion between embryonic cells and maternal uterine cells, as
part of the physiologic response to implantation [22, 23].
Thus, it is crucial to know whether and when DCs produce
IL-10 and/or IL-12 cytokines in the specific environment
of the feto-maternal interface. Indeed, the production of IL-
12 by DCs is required to induce T-cell priming and might
represent a switch to immunogenicity, whereas IL-10 pro-
duction by these cells is supposed to induce a tolerogenic
(or at least regulatory) and thus pregnancy-protective re-
In this study, we report that the majority of uterine DCs
were myeloid, as identified by their negativity for CD8?
supporting the pregnancy-protective role of DCs. Further-
more, we determined that intracellular presence of IL-10 by
DC was significantly higher than IL-12 during most of the
gestation. With respect to discussion point 2, this bias to-
ward IL-10 production at the uterine level seems to be the
key to induction of tolerance because this cytokine acts as
an inhibitor of the immune response in different ways: by
suppressing T cells itself ; by inducing differentiation
to regulatory T cells [25, 26]; or by inhibiting DC terminal
differentiation [27, 28], skewing them toward a tolerogenic
However, another interesting finding of this study was
the transient increase in the percentage of CD8??DC uter-
ine cells in early gestation, namely on GD 5.5, which was
accompanied by a transitory decrease in the relative num-
ber of IL-10-producing DCs. The remarkable plasticity in
the ability to induce Th1 or Th2 cytokines, temporal reg-
ulation, and subtle discrimination of antigen stimuli by DCs
has been recognized . Therefore, we suggest that fetal
antigens could be stimulating CD8??DC uterine cells to
produce Th1 cytokines during the peri-implantation period
of pregnancy. Thus, DCs seem to contribute to the devel-
opment of an adequate environment during the implantation
period. Afterward, a Th2-biased cytokine pattern is pre-
dominant, which mediates the communication between em-
bryonic cells and maternal uterine cells and the establish-
ment of pregnancy [19–23]. We cannot conclude that
CD8??DCs are responsible for the production of Th1-cy-
tokines during peri-implantation because recently published
data demonstrated disparate roles of DC subsets in various
experimental models [31, 32]; nevertheless, this observa-
tion might provide a clue regarding discussion point 2.
Furthermore, we observed that some part of uterine DCs
constitutively express MHC class II, indicating that these
resident DCs possess some degree of maturation. Recently,
Colledge and coworkers reported that constitutive peptide-
MHC class II complex generation occurs in DCs in im-
munologically quiescent situations and that antigen presen-
tation by nonactivated DCs might play a role in the induc-
tion of tolerance . Worthy of note is the finding of a
downregulation of MHC class II expression on the surface
of uterine DCs from GD 5.5 until GD 8.5. A recent review
by Lutz and Schuler  about the state of DC maturation
and the ability to induce tolerance or immunity gives some
hints to understand this phenomenon: according to their
model, DCs expressing low quantities of MHC class II are
supposed to induce T-cell anergy in the absence of antigen
stimulation. Therefore, the observation of DCs expressing
low levels of MHC class II during this period of gestation
might be related to fetal acceptance, which might give an
explication to question 3.
Comparing the relative numbers of CD11c?cells in blood
and locally, we observed lower cell numbers for CD11c?
cells in blood, suggesting a focal point of function for DCs
in the local environment. This agrees with published data
where DCs are considered to be responsible for tolerance of
antigens in mucosal surfaces . Moreover, the phenotype
of blood DCs revealed a higher grade of maturation com-
pared with uterine DCs as identified by their expression of
MHC II molecules and the total amount of cytokine pro-
duction. This disparity of the maturation status between
blood and uterine DCs suggests different roles in the main-
tenance of pregnancy between blood and locally in the uterus
and might provide an explanation of question 4.
In conclusion, we have characterized the phenotype and
function of CD11c?cells in the uterus and in blood during
pregnancy. Features described here, as the varying number
of resident DC subsets, changes in the expression pattern
of IL-10 and IL-12 cytokines and MHC II molecules by
DCs, demonstrate that DCs represent a cell population with
unique properties required for the maternal tolerance of the
fetus. Therefore, this study provides a basis for further re-
search and suggests that examining the function of DCs and
DC subsets may be relevant to further understanding of the
immunology at the feto-maternal interface.
DENDRITIC CELLS DURING MURINE PREGNANCY
We are very grateful to Petra Moschansky, Ruth Pliet, Petra Busse,
and Evelin Hagen for their technical assistance, Dr. Judith Kandil and
Justin Manuel for their support in mice preparation, and Dr. David Clark
for fruitful discussions.
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