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*
Institut National de la Santé et de la Recherche Médicale Unité 437 and Institut de Transplantation et de Recherche en Transplantation, Nantes, France;
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and
Department of Nephrology and Clinical Immunology, Nantes University Hospital, Nantes, France
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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. Therefore, rat DCs contain a subset of naturally
cytolytic cells that could play a role in both innate and acquired
immune responses. Together with our previous report, these data suggest
that rat DCs can use two mechanisms of cytotoxicity depending on their
maturation/activation state. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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-, whereas a smaller subset expresses the
CD8 molecule together with high levels of the DEC-205 receptor
(3). Recent reports indicate these DC subsets differ in
their Th cell stimulatory activity. CD8+ splenic
DCs induced the differentiation of Th1 cells, whereas
CD8- DCs promoted the differentiation of Th2
cells (4). CD8+ splenic DCs have
also been shown to exhibit a negative regulatory function on
CD8+ and CD4+ T cells
(5, 6). In humans, different subsets of DCs have been
described in blood. DC1s are monocyte-derived DCs that produce large
quantities of IL-12 upon stimulation and promote the differentiation of
Th1 cells (7). DC2s are a less abundant subset of DCs that
display features of the lymphoid lineage and express high levels of
IL-3R. They promote the differentiation of Th2 cells
(7). More recently, it was shown that a subset of blood
DCs, closely related to the myeloid-related DC1s cells, exhibited
cytotoxic activity against tumor cells using the TNF-related
apoptosis-inducing ligand (TRAIL)-TRAIL-R pathway (8).
Previously, we showed that overnight cultured splenic, but not lymph
node (LN) or thymic DCs exhibited an NK-like cytotoxic activity in
rats, as demonstrated by their ability to kill the YAC-1 cell line in
vitro (9). Subsets of rat DCs have been described in
pseudo-afferent intestinal lymph. CD4+ DCs that
also express the Ag recognized by the OX41 mAb are better stimulators
of T cell proliferation than the
CD4-/OX41- subset
(10). Thymic DCs also vary in their expression of markers
such as CD5 and CD4 (11). In this work, we further define
the phenotype and function of the cytotoxic subset of rat DCs in
lymphoid organs. DCs were purified from lymphoid organs (spleen, LN,
and thymus) using the OX62 mAb that recognizes an integrin expressed on
rat DCs (12). This procedure allowed us to use freshly
extracted DCs without the overnight culture step, which could result in
the stimulation of nonphysiological functions. We identified the
cytotoxic subset of DCs in rat spleen as the
CD4-/OX41- cells that are
poorly represented in LN and thymus. The killing activity was
Ca2+-independent, but did not appear to be mediated by TNF
family members Fas ligand (FasL), TRAIL, or TNF-.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Sprague Dawley and Lewis rats were obtained from the Center d’Elevage Janvier (Le genest-Saint-Isle, France) and were used at 6–10 wk old.
Reagents
The Fas.Fc fusion molecule was kindly provided by Dr. Yongwon Choi (The Rockefeller University, New York, NY). Concanamycin A and EGTA were obtained from Sigma Aldrich (St. Louis, MO). Collagenase D was from Boehringer Mannheim (Mannheim, Germany).
Monoclonal Abs
The following mouse anti-rat mAbs obtained from the European
Collection of Cell Culture (Salisbury, UK) were used in
cytofluorometric studies and cell sorting after coupling to FITC,
biotin, or PE (Bioatlantic, Nantes, France): OX6 (MHC class II), W3/25
(CD4), R7.3 (TCRß), OX7 (Thy-1, CD90), OX19 (CD5), OX33 (CD45R on
B cells), OX42 (CD11c), OX41 (glycoprotein 110 on macrophages,
granulocytes, and some DCs), OX8 (CD8), OX62 (an integrin on DCs),
and ED3 (sialoadhesin). FITC-conjugated anti-CD3 (clone G4.18),
anti-CD86/B7-2 (clone 24F), and hamster anti-mouse CD40
(cross-reacting with rat CD40) mAbs were purchased from PharMingen (San
Diego, CA). FITC anti-CD161a (NKRP1A) was purchased from Serotec
(Oxford, U.K.). MFL4, a neutralizing anti-mouse and rat FasL mAb
(13), and DR5-Ig fusion molecule (14) were
previously described, and a neutralizing anti-rat TNF- mAb was
purchased from R&D Systems (Minneapolis, MN).
Cell lines
Murine TRAIL (mTRAIL)- and mock-transfected 2PK-3 cells were described previously (14) and cultured in complete RPMI. To obtain stable transfectants for rat FasL, RT-PCR-generated rat FasL cDNA was cloned in pMKITNeo vector and transfected in L5178Y cells, as described (13). YAC-1, P815, K562, A20, and L929 target cells were obtained from the European Collection of Cell Culture and cultured in complete RPMI.
Cell preparation
DCs. Lymphoid organs (spleen, LN, thymus) were minced and digested in 2 mg/ml collagenase D in RPMI, 1% FCS for 30 min at 37°C. EDTA at 10 mM was added during the last 5 min, and the cell suspension was then pipetted up and down several times and filtered. Cells were washed once in PBS/EDTA, 2 mM/1% FCS, and low density cells were obtained after centrifugation on 14.5% Nycodenz gradient, as previously described (9). Cells were then incubated with a saturating concentration of biotin-conjugated OX62 mAb at 4°C for 20 min, washed twice, and then mixed with streptavidin-conjugated microbeads, following manufacturer’s instructions (Miltenyi Biotec, Paris, France). Positive selection was performed on MiniMacs type positive selection columns (Miltenyi Biotec). Although positive selection of DCs was also effective from bulk collagenase-digested lymphoid suspensions (data not shown), the first step of DC enrichment was performed to reduce the volume of magnetic beads needed.
T cells.
CD4+ and CD8+ T cells were
prepared from LN cells by negative selection of class
II+, Ig+,
CD161+, and CD8+ or
CD4+ cells, respectively, followed by
anti-mouse IgG-coated magnetic beads (Dynal, Oslo, Norway). Purity
was routinely 
98% and 90% for CD4+ and
CD8+ T cells, respectively.
NK cells. Spleen cells were depleted of class II+ and surface Ig+ cells (Dynal), and NK cells were sorted by FACS using the 3.2.3 mAb.
Cytofluorometry and cell sorting
For cytofluorometric analyses, 5 x 104 cells were incubated with PE-conjugated OX6 or W3/25 mAb together with another FITC-conjugated mAb for 20 min at 4°C. Cells were washed twice and analyzed on a FACScalibur (Becton Dickinson, Mountain View, CA). For cell sorting of CD4+ and CD4- subsets of splenic DCs, OX62+ cells were incubated with OX6-PE- and W3/25-FITC-conjugated mAbs and sorted on FACSvantage (Becton Dickinson).
Mixed leukocyte reaction
Increasing numbers of allogenic DCs were cultured with 5 x 104 purified total, CD4+ or CD8+ T cells in round-bottom 96-well plates in a final volume of 200 µl for 3 days at 37°C, 5% CO2, and for the last 8 h in the presence of 0.5 µCi [3H]TdR (Amersham, Les Ulis, France). The cells were then harvested on glass fiber filters, and [3H]TdR incorporation was measured using standard scintillation procedure (Packard Instruments, Meriden, CT).
Cytotoxicity assays
Cytotoxic activity of DC populations was assessed in a standard 6-h 51Cr release assay using the YAC-1, P815, K562, L929, and A20 cell lines as targets. Briefly, target cells were labeled with sodium 51Cr for 45 min at 37°C in complete medium. Serial dilutions of effector cells in complete medium were mixed with 3000 target cells in V-bottom 96-well plates in triplicates, centrifuged 3 min at 1500 x g, and incubated for 6 h at 37°C, 5% CO2. The supernatants were harvested and 51Cr release was determined (Packard Instruments) using standard scintillation procedures. Specific release was calculated as 100 x (experimental release - spontaneous release)/(maximum release - spontaneous release).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Because the overnight culture period that is used during the usual
DC purification procedure promotes DC maturation (15), we
focused in this study on freshly extracted DCs. Highly purified DC
populations were prepared by positive selection using the OX62 mAb,
which recognizes the E2 subunit of an integrin (16)
specifically expressed on rat DCs (12). Although it has
been found that the OX62 mAb also recognized some 
T cells
(12, 16), we found that these cells in LN were OX62
negative (data not shown). In four preliminary experiments, we found
that 80%, 55%, and 70% of splenic, LN, and thymic DCs, respectively,
express the integrin recognized by the OX62 mAb (data not shown).
Whether OX62- DCs represent a specific subset or
whether the OX62 integrin is sequentially regulated during DC
differentiation and maturation is still unknown. However, preliminary
experiments have shown the same distribution of DC subsets (see below)
in both OX62+ and OX62-
DCs (data not shown).
The phenotype of OX62-sorted cells was analyzed by FACS after double
staining using PE-conjugated anti-class II mAb (OX6-PE) and
FITC-conjugated mAbs. As shown in Fig. 1
, more than 90% of cells expressed high levels of class II MHC molecules
and the integrin recognized by the OX62 mAb (dot plots at the
bottom left), and are therefore DCs. Contaminant cells that
routinely represented 1–8% of total cells were mostly T and B cells,
whereas sialoadhesin-positive cells (macrophages), NK cells
(CD161a- and class II-
cells), never exceeded 2%. Marginal expression of CD3 was observed on
DCs expressing very high levels of MHC class II molecules in LN and
thymus (Fig . 1, B and C). The restricted isoform
of CD45 recognized by the OX33 mAb and expressed by rat B cells was
also detected on the surface of LN and thymic DCs (Fig. 1, B
and C). Whether these molecules are really expressed or just
picked up by DCs is unknown.
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We previously reported that splenic, but not LN or thymic DCs
exhibited a cytotoxic activity against the NK-sensitive cell line YAC-1
(9). However, these experiments were performed after a
step of overnight culture whose physiological significance is not
clear. We therefore analyzed the cytotoxic activity of freshly
extracted DCs. As shown in Fig. 2A, splenic DCs very
efficiently killed YAC-1 cells, whereas LN and thymic DCs were poorly
cytotoxic. Interestingly, this cytotoxic activity against YAC-1 cells
was close to that exhibited by purified spleen NK cells at the same E:T
cell ratio (see Fig. 6). The T cell stimulatory activity of DCs was
assessed in allogenic MLR. As shown on Fig. 2B, LN and
thymic DCs were slightly better stimulator of allogenic T cells
proliferation than splenic DCs. Several target cells commonly used to
test NK cytotoxicity were also assessed against DCs. Freshly extracted
splenic DCs were also moderately cytotoxic toward NK-sensitive K562
cells, and A20 cells but not LAK-sensitive P815 cells and the L929
fibroblast cell line (Fig. 3).
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These previous results suggest that the cytotoxic activity of rat
DCs was dependent on a subset of DCs present in spleen, but not LN and
thymus. We therefore double stained freshly extracted DCs for MHC class
II and several other markers allowing for the definition of
subpopulations (Fig. 1
). Several DC subsets could be defined based on
levels of expression of MHC class II, CD4, CD5, OX41, CD90, CD161a, and
CD11c molecules (Figs. 1 and 4). Unlike
in mice (3), the expression of the CD8 molecule did not
discriminate DC subpopulations, as all splenic DCs in rats were
CD8- (Fig. 1A). In contrast and as
previously shown previously in rat lymph (10), two subsets
of splenic DCs could be defined based on the expression of CD4 (Figs. 1A and 4). The main subset (80%) was class
II++, CD4-,
CD5-, OX41-,
CD90-/+, CD11c+++, and
CD161a+, and the minor subset (15%) was class
II+, CD4++,
OX41++, CD90+/+++,
CD11c+++, and CD161a++
(Figs. 1A and 4). The cells of the minor subset were smaller
(data not shown) and expressed lower levels of OX62 than the
CD4- subset. A third and minor (<5%) subset
was defined as class II+++,
CD4-, CD90-,
CD11c++, and CD161a-/+
(Fig. 1A). Unlike the two other subsets that display an
immature phenotype (no CD86 expression), the class
II+++ cells express low levels of costimulatory
molecules CD86 and CD40. However, levels of class II, CD86, and CD40
molecule expression were strongly up-regulated on all spleen and LN DCs
upon spontaneous maturation that occurs during overnight culture (data
not shown).
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B). The
CD4-/OX41-/CD5-
and
CD4+/OX41+/CD5+
DC subsets that we found in spleen represent 19% and 33% of LN DCs,
respectively. The third and major subset (46%) of LN DCs expresses
very high levels of MHC class II molecules (Fig. 1B),
does not express CD161a, expresses lower levels of CD11c than other
DCs, and expresses low levels of CD86 and CD40. This subset could also
be separated in
CD4+/CD90+++ and
CD4-/CD90-/+ cells. In
thymus, previously described subsets were not clearly observed (Fig. 1C). All thymic DCs express CD90, but most of the cells were
CD4-, indicating that, unlike in spleen and LN,
these two markers are not coexpressed (see Fig. 4). However, thymic DCs
segregated in OX41+ and
OX41- cells. They were also homogeneously
CD161a+ and OX62+, and the
cells expressing the higher level of MHC class II also express CD86
and CD40. Identification of cytotoxic DCs in spleen as the CD4- subset
To determine which subset of splenic DCs exhibits a killing
activity, splenic DCs were double labeled with PE-conjugated OX6 mAb
(MHC class II) and FITC-conjugated W3/25 mAb (CD4) and sorted on a
FACSvantage in OX6++ CD4-
and OX6++ CD4+ subsets
(Fig. 5). Fig. 6 shows clearly that the
CD4-, but not the CD4+
subset exhibited a cytotoxic activity. To investigate whether this
cytotoxic function could play a role during Ag presentation to T cells
by DCs, we performed MLR. Interestingly, CD4+
splenic DCs were slightly better stimulator of both
CD4+ and CD8+ T cell
proliferation than CD4- cells (Fig. 7). This was mostly observed at
high ratio of stimulator:responder cells. However, FACS-sorted
CD4- splenic DCs were unable to kill resting or
activated, syngenic or allogenic, CD4+ or
CD8+ T cells in vitro (data not shown).
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mediated
In our previous report, we showed that the cytotoxic activity of
overnight cultured splenic DCs was strictly dependent on
Ca2+ (9), suggesting a mechanism of
exocytosis of perforin- and granzyme-containing lytic granules, as
described in NK and CD8+ T cells (17, 18). Mechanisms of cytotoxicity of freshly extracted splenic DCs
were therefore studied and compared with those of purified splenic NK
cells. Surprisingly, the cytotoxic activity of freshly extracted
splenic DCs was not inhibited by EGTA, indicating a
Ca2+-independent mechanism (Fig. 8A). Previous studies have
shown that concanamycin A, an ATPase inhibitor, specifically
inactivated perforin by increasing pH in intracellular lytic granules
(19). Despite the absence of an effect of EGTA,
concanamycin A strongly, but not completely, inhibited the cytotoxic
activity of splenic DCs (Fig. 8A). In contrast, the
cytotoxic activity of purified fresh spleen NK cells against YAC-1 was
inhibited to the same extent by EGTA and concanamycin A, indicating
that rat spleen NK cells mainly used the perforin pathway to kill the
YAC-1 cells (Fig. 8B). Moreover, the cytolytic activity of
splenic DCs against YAC-1 cells was strongly inhibited by
cycloheximide, indicating that the killing mechanism requires protein
synthesis in DCs (data not shown).
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A). The killing of YAC-1 by
splenic DCs was not significantly inhibited by a neutralizing mAb
against FasL (Fig. 9B), nor by the fusion molecule Fas.Fc
(data not shown). Moreover, only a small subset of A20 cells that are
highly sensitive to Fas-induced apoptosis (Fig. 9A) was
killed by splenic DCs (see Fig. 3), and this killing was not inhibited
by Fas.Fc or the anti-FasL MFL4 mAb (data not shown). As previously
shown (14), YAC-1 cells were not killed by
mTRAIL-transfected 2PK-3 cells (Fig. 9A). Moreover, spleen
DC-mediated killing of YAC-1 cells was not inhibited by DR5-Ig (Fig. 9B). In contrast, TRAIL-sensitive L929 cells were killed by
mTRAIL transfectants (Fig. 9A and Ref. 14), but
not efficiently by splenic DCs (Fig. 3).
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in a
5-h assay (Fig. 9A), and neutralizing TNF- during the
assay did not inhibit cytotoxicity (Fig. 9B). Taken
together, these data suggest that the cytotoxic activity of fresh
splenic DCs is not dependent on FasL, TRAIL, or TNF-. Moreover, it
was not mediated by a soluble molecule, as no cytotoxic activity
against YAC-1 cells was detected in the supernatant of a splenic DC
cytotoxic assay (data not shown). Finally, paraformaldehyde-fixed
splenic DCs lost their cytotoxic activity, arguing against the
involvement of a preformed membrane molecule (data not shown). |
Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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DCs with cytotoxic activity have been described previously in several
species, suggesting that this function is conserved and might play a
role in immune responses. In mouse, a subset of splenic DCs expressing
the CD8 molecule and exhibiting lymphoid feature has been shown to
mediate apoptosis of CD4+ T cells through the
expression of FasL (5). However, these data have proven
difficult to reproduce (our unpublished observation). Lu et al.
(20) also found that murine DCs derived in vitro from
marrow progenitors in the presence of GM-CSF and IL-4 express FasL and
could induce apoptosis in Jurkat T cells. A subset of human blood DCs
with myeloid feature has recently been shown to be cytotoxic toward
several tumor cell lines through the expression of TRAIL, another
apoptosis-inducing molecule (8). These human DCs need,
however, to be activated by IFN- or IFN- to express TRAIL and
acquire the ability to kill. Interestingly, type I IFNs also
up-regulated TRAIL expression on human T cells (21),
suggesting that this effect could be involved in the antitumor activity
of these cytokines. Unlike in human DCs, the cytotoxic activity of
splenic DCs in rats did not require any stimulation, suggesting that
this function could be instrumental in vivo, as described for NK cells.
In addition, on a per cell basis, splenic DCs were almost as efficient
as NK cells in killing YAC-1 cells in vitro (Fig. 8).
The major difference found in the cytotoxic activity of DCs prepared from spleen, LN, or thymus is likely to reflect the relative distribution of this CD4- cytotoxic subset in lymphoid organs. Indeed, these cells were abundant in spleen (>85% of total DCs), but rare in LN (<20% of total DCs) or thymus. Moreover, we could not detect such a cytotoxic activity in immature or mature bone marrow-derived or blood monocyte-derived DCs, despite a phenotype almost similar to the one we described in this work for the CD4-/OX41- splenic DC subset (data not shown).
In our previous report, we showed that the cytotoxic activity of overnight cultured splenic DCs was Ca2+ dependent, and therefore probably mediated by exocytosis of perforin-containing lytic granules (9). The killing activity of freshly prepared splenic DCs was not inhibited by EGTA, which is known to antagonize both lytic granule exocytosis and perforin polymerization. However, DC-mediated cytotoxicity was strongly reduced by concanamycin A, a reagent known to inactivate perforin by increasing pH in lytic granules (19). It is possible that independent of its perforin inactivation properties, concanamycin A could have effects on other intracellular proteins involved in cytotoxic function and whose function might also be pH dependent. The possibility that concanamycin A could have an effect on YAC-1 target cells is excluded by the fact that it did not protect them against NK cell-mediated killing.
Calcium-independent mechanisms of cytotoxicity are mainly related to
molecules of the TNF superfamily that induce apoptosis in target cells
through interaction with a death domain-containing specific receptor
(22). The fact that fixed splenic DCs were not cytotoxic
indicated that the killing was not mediated by a preformed membrane
molecule. However, apoptosis-inducing molecules could have been
synthesized during the cytotoxicity assay. Indeed, the inhibition of
DC-mediated cytotoxicity by cycloheximide strongly suggests that the
molecule(s) involved in YAC cell killing needs to be synthesized during
the in vitro assay. Although both FasL and TRAIL have been shown to
mediate the induction of apoptosis in target cells by murine or human
DCs, respectively (5, 8, 20), our results and those of
Kayagaki et al. (14) strongly suggest that none of these
molecules are involved in splenic DC-mediated cytotoxicity in rat.
TNF- was probably not involved, because the cytotoxicity was not
inhibited by a neutralizing mAb against TNF-. The role of recently
cloned members of the TNF-R family containing a death domain such as
DR3 (23) and DR6 (24) will be tested.
Together with our previous report (9), our data suggest
that rat splenic DCs have the capacity to kill YAC-1 cells using both a
Ca2+-dependent and a
Ca2+-independent mechanism. Interestingly,
depending on their maturation stage, NK cells can also exhibit
different mechanisms of cytolysis, and granule release-dependent
cytotoxicity is present in mature, but not immature NK cells
(25). Our preliminary results indicated that freshly
extracted OX62+ spleen DC lose their
Ca2+-independent cytotoxic activity upon
overnight culture and that the residual cytolytic function turns to be
Ca2+ dependent. However, the cytolytic function
of overnight cultured OX62+ spleen DC was much
lower than the one we described in our previous report
(9). This difference might be due to the very short
t1/2 of freshly extracted
OX62+ DC in culture. In contrast, these
discrepancies could be related to the different DC purification
procedures that we used in these two studies, and that might
preferentially enrich for different DC subsets. These hypotheses are
currently being tested.
Rat CD4+ and CD4- DC subsets have been previously described by Liu et al. (10) in the pseudo-afferent intestinal lymph. The same authors suggested that the CD4+ and CD4- subsets in rat exhibited lymphoid and myeloid features, respectively (10). In support of this hypothesis, we have shown that the CD4+ and noncytotoxic subset of splenic DCs expressed the lymphoid-related markers CD90 and CD5. Our study identified another subset of DCs in LN expressing high levels of class II Ag, and low levels of CD11c and CD4 that might also be lymphoid derived. We have shown that the cytotoxic subset of DCs was the main subset in spleen, whereas these cells were rare in LN and thymus, in which lymphoid DCs are thought to reside. The potential in vivo role of these cytotoxic DCs remains unknown. One hypothesis is that these cells are involved in tolerance rather than immunity and act by inducing cell death in T cells. However, although CD4+ splenic DCs are better stimulator of T cells than CD4- ones (Ref. 10 and this report), this is probably not related to the cytotoxic activity of CD4- splenic DCs, as they were unable to kill T cells in vitro.
Huang et al. (26) recently reported that a discrete subpopulation of DCs isolated from rat intestinal lymph was specialized in the transport of apoptotic cells from intestine to draining LN. DCs containing apoptotic bodies derived from injected allogenic lymphocytes have also been described previously in rat spleen by Fossum and Rolstad (27). This recent finding may provide a mechanism by which immature DCs tolerize T cells to self Ags derived from apoptotic cells throughout the body (28). It is important to note that this subset of DCs appears to be phenotypically identical with the cytotoxic subset of splenic DCs that we described in this study (i.e., CD4-/OX41- cells). It would be interesting to test whether the CD4-/OX41- subset isolated from rat intestinal lymph also exhibits a cytolytic function in vitro. We are currently investigating whether the killing of target cells by DCs is followed by the phagocytosis of their victims and efficient presentation of target cell-derived Ags to T cells (29). Cytotoxic DCs would therefore create an immediate link between innate and adaptive immunity and may be a tool for antitumor immunotherapy. For this purpose, a large panel of tumor cells is currently being tested for their sensitivity to the cytolytic activity of DCs. However, in vivo, this function may not result in the induction of an immune response. Indeed, DCs need to mature to acquire the capacity to stimulate naive T cells (1). Two recent papers have shown that the ingestion of apoptotic cells or bodies by immature DCs does not induce their maturation (30, 31), again suggesting that this source of Ag could be important for tolerance rather than immunity. Because spontaneous maturation of splenic DCs occurs in vitro after their extraction from lymphoid tissues, an in vivo model will be required to assess the role of this cytotoxic subset of DCs in tolerance and immunity.
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Acknowledgments |
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Footnotes |
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2 B.T. and C.V. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Régis Josien, Department of Nephrology and Clinical Immunology, Nantes University Hospital, 30 boulevard Jean Monnet, 44093 Nantes Cedex 1, France.
4 Abbreviations used in this paper: DC, dendritic cell; FasL, Fas ligand; LN, lymph node; TRAIL, TNF-related apoptosis-inducing ligand; mTRAIL, murine TRAIL.
Received for publication March 31, 2000. Accepted for publication July 19, 2000.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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F.-X. Hubert, C. Voisine, C. Louvet, J.-M. Heslan, A. Ouabed, M. Heslan, and R. Josien Differential Pattern Recognition Receptor Expression but Stereotyped Responsiveness in Rat Spleen Dendritic Cell Subsets J. Immunol., July 15, 2006; 177(2): 1007 - 1016. [Abstract] [Full Text] [PDF]
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 F. De Bernardis, R. Lucciarini, M. Boccanera, C. Amantini, S. Arancia, S. Morrone, M. Mosca, A. Cassone, and G. Santoni Phenotypic and Functional Characterization of Vaginal Dendritic Cells in a Rat Model of Candida albicans Vaginitis Infect. Immun., July 1, 2006; 74(7): 4282 - 4294. [Abstract] [Full Text] [PDF]
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 U. I. Chaudhry, S. C. Katz, T. P. Kingham, V. G. Pillarisetty, J. R. Raab, A. B. Shah, and R. P. DeMatteo In vivo overexpression of Flt3 ligand expands and activates murine spleen natural killer dendritic cells FASEB J, May 1, 2006; 20(7): 982 - 984. [Abstract] [Full Text] [PDF]
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N. Degauque, D. Lair, A. Dupont, A. Moreau, G. Roussey, F. Moizant, F. X. Hubert, C. Louvet, M. Hill, F. Haspot, et al. Dominant Tolerance to Kidney Allografts Induced by Anti-Donor MHC Class II Antibodies: Cooperation between T and Non-T CD103+ Cells J. Immunol., April 1, 2006; 176(7): 3915 - 3922. [Abstract] [Full Text] [PDF]
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B. Trinite, C. Chauvin, H. Peche, C. Voisine, M. Heslan, and R. Josien Immature CD4-CD103+ Rat Dendritic Cells Induce Rapid Caspase-Independent Apoptosis-Like Cell Death in Various Tumor and Nontumor Cells and Phagocytose Their Victims J. Immunol., August 15, 2005; 175(4): 2408 - 2417. [Abstract] [Full Text] [PDF]
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E. L. Turnbull, U. Yrlid, C. D. Jenkins, and G. G. MacPherson Intestinal Dendritic Cell Subsets: Differential Effects of Systemic TLR4 Stimulation on Migratory Fate and Activation In Vivo J. Immunol., February 1, 2005; 174(3): 1374 - 1384. [Abstract] [Full Text] [PDF]
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U. Schleicher, A. Hesse, and C. Bogdan Minute numbers of contaminant CD8+ T cells or CD11b+CD11c+ NK cells are the source of IFN-{gamma} in IL-12/IL-18-stimulated mouse macrophage populations Blood, February 1, 2005; 105(3): 1319 - 1328. [Abstract] [Full Text] [PDF]
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F.-X. Hubert, C. Voisine, C. Louvet, M. Heslan, and R. Josien Rat Plasmacytoid Dendritic Cells Are an Abundant Subset of MHC Class II+ CD4+CD11b-OX62- and Type I IFN-Producing Cells That Exhibit Selective Expression of Toll-Like Receptors 7 and 9 and Strong Responsiveness to CpG J. Immunol., June 15, 2004; 172(12): 7485 - 7494. [Abstract] [Full Text] [PDF]
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C. Guillot, S. Menoret, C. Guillonneau, C. Braudeau, M. G. Castro, P. Lowenstein, and I. Anegon Active suppression of allogeneic proliferative responses by dendritic cells after induction of long-term allograft survival by CTLA4Ig Blood, April 15, 2003; 101(8): 3325 - 3333. [Abstract] [Full Text] [PDF]
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C. Voisine, F.-X. Hubert, B. Trinite, M. Heslan, and R. Josien Two Phenotypically Distinct Subsets of Spleen Dendritic Cells in Rats Exhibit Different Cytokine Production and T Cell Stimulatory Activity J. Immunol., September 1, 2002; 169(5): 2284 - 2291. [Abstract] [Full Text] [PDF]
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C. S. Brissette-Storkus, J. C. Kettel, T. F. Whitham, K. M. Giezeman-Smits, L. A. Villa, D. M. Potter, and W. H. Chambers Flt-3 ligand (FL) drives differentiation of rat bone marrow-derived dendritic cells expressing OX62 and/or CD161 (NKR-P1) J. Leukoc. Biol., June 1, 2002; 71(6): 941 - 949. [Abstract] [Full Text] [PDF]
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D. Masse, C. Voisine, F. Henry, S. Cordel, I. Barbieux, R. Josien, K. Meflah, M. Gregoire, and B. Lieubeau Increased Vaccination Efficiency with Apoptotic Cells by Silica-induced, Dendritic-like Cells Cancer Res., February 1, 2002; 62(4): 1050 - 1056. [Abstract] [Full Text] [PDF]
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N. Vanderheyde, E. Aksoy, Z. Amraoui, P. Vandenabeele, M. Goldman, and F. Willems Tumoricidal Activity of Monocyte-Derived Dendritic Cells: Evidence for a Caspase-8-Dependent, Fas-Associated Death Domain-Independent Mechanism J. Immunol., October 1, 2001; 167(7): 3565 - 3569. [Abstract] [Full Text] [PDF]
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L. M. Alonso-C., J. J. Munoz, and A. G. Zapata Delineation of Intrathymic T, NK, and Dendritic Cell (DC) Progenitors in Fetal and Adult Rats: Demonstration of a Bipotent T/DC Intermediate Precursor J. Immunol., October 1, 2001; 167(7): 3635 - 3641. [Abstract] [Full Text] [PDF]
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P.-O. Vidalain, O. Azocar, H. Yagita, C. Rabourdin-Combe, and C. Servet-Delprat Cytotoxic Activity of Human Dendritic Cells Is Differentially Regulated by Double-Stranded RNA and CD40 Ligand J. Immunol., October 1, 2001; 167(7): 3765 - 3772. [Abstract] [Full Text] [PDF]
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T. Saiki, T. Ezaki, M. Ogawa, K. Maeda, H. Yagita, and K. Matsuno In vivo roles of donor and host dendritic cells in allogeneic immune response: cluster formation with host proliferating T cells J. Leukoc. Biol., May 1, 2001; 69(5): 705 - 712. [Abstract] [Full Text]
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