| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
evi
*
*
Department of Immunology, Erasmus University, Rotterdam, The Netherlands;
CNRS ERS 107, Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Université Pierre et Marie Curie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; and
Department of Cell Biology and Immunology, Free University, Amsterdam, The Netherlands
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
+. Notably, both
populations, when freshly isolated, express the macrophage markers
F4/80, BM8, and Mac-1. To study the phagocytic capacity of these cells,
we employed the macrophage "suicide" technique by injecting
liposomes loaded with clodronate i.v. Marginal DC, but not IDC, were
eliminated by this treatment. Phagocytosis of DiI-labeled liposomes by
DC confirmed this finding. The two DC populations differed
significantly with regard to their turnover rates, as studied in a
transgenic mouse model of conditional depletion of DC populations with
high turnover. In these mice, marginal DC were completely eliminated,
but the IDC population remained virtually intact. From these data we
conclude that the marginal DC population has a high turnover, in
contrast to the IDC population. Taken together, the present results
indicate that marginal DC and IDC represent two essentially distinct
populations of DC in the mouse spleen. They differ not only in
location, but also in phenotype, phagocytic ability, and turnover. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
expression, suppress immune responses by
inducing apoptosis of CD4+ T cells or limiting IL-2
production by CD8+ T cells (8, 9). In the mouse spleen, two subpopulations of DC have been shown in anatomically distinct locations. A minor population of so-called interdigitating cells (IDC) is located in the white pulp T cell zone, the inner periarteriolar lymphocyte sheath, and a larger population of marginal DC is found at the border of marginal zone and splenic red pulp (10). The IDC population was described more than two decades ago (11) and was thought to be the primary stimulating cell type in T cell responses. More recently, the larger marginal DC population was identified (10, 12). It was recognized that these cells, constituting about 75% of isolated spleen DC, may be held responsible for most of the stimulating activities of splenic DC measured in in vitro assays. It remains unclear at present how this stimulating function may be exerted in vivo, since marginal DC are not located in the area where T cell responses are thought to take place. Related to this, questions also remain concerning the ability of DC to take up Ag, especially in vivo. Based on early in vitro studies, the endocytic ability of DC was thought to be very limited (reviewed by Steinman and Swanson, 13 . However, later it was recognized that in vitro monocyte-derived DC have significant macropinocytic activity (14). In mouse bone marrow (BM) cultures, immature stages of DC development were found to phagocytose particles, including bacteria. This activity is lost upon terminal maturation of DC (15). Information about in vivo phagocytic activity of DC or their precursors is scarce, although recently rat hepatic lymph DC were shown to internalize i.v.-injected carbon or latex particles (16).
In a previous study, we described the DC expression of aminopeptidase N/CD13, recognized by mAb ER-BMDM1 (17). Others found this enzyme to be a marker for APC, and recently it was implicated in the extracellular trimming of MHC-bound peptides (18, 19). In addition to the classic IDC in the white pulp, a population of nonlymphocytic cells located in patches at the border of marginal zone and red pulp was recognized by ER-BMDM1 (17). On the basis of their expression of genuine macrophage markers such as F4/80 and BM8, detected by immunofluorescence double labeling, we then suggested the designation of the latter cells as "marginal red pulp macrophages." In the present study, we compared splenic DC and CD13+/ER-BMDM1+ marginal red pulp macrophages with respect to their phenotype and phagocytic function. We also compared their turnover, using a model for conditional depletion of DC, based on the selective expression in DC of herpes simplex thymidine kinase in a transgenic mouse (20, 21). Treatment of these HIV-1 long terminal repeat-herpes simplex virus type 1 thymidine kinase (LTR-TK) transgenic mice, or mice made chimeric after engraftment of transgenic BM, with ganciclovir (GCV) specifically induces killing of DC, which actively synthesize DNA, but not of resting DC.
We show that the CD13+/ER-BMDM1+ marginal red pulp macrophages are actually identical to the previously identified marginal DC. These cells are essentially distinct from the splenic white pulp IDC. Marginal DC are able to phagocytose particulates in vivo, express markers characteristic of both DC and macrophages, and have a high turnover. In contrast, IDC are not phagocytic in vivo and have slow turnover.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
C57BL/6 mice were used between 6 and 20 wk of age. In some DC isolation experiments, C57BL/10 mice (20 wk of age) were used with similar results. Mice were kept under clean conditions (specific pathogen free, grade 5). Animals were killed by CO2 exposure and spleens were removed for cell isolation or histology.
Derivation of HIV1-LTR/HSV1-TK transgenic mice (abbreviated as LTR-TK
mice) has been described (20). These mice, originally (C57BL x
DBA/2)F2, were back-crossed to a DBA/2 genetic background.
LTR-TK BM chimeric mice were generated by lethal irradiation (1200 rad
-irradiation) of 8-wk-old male DBA/2 mice and subsequent transfer of
BM cells from LTR-TK transgenic mice. Four months after BM
transplantation, chimeric mice were treated with GCV (see below) or
sham-treated during 7 days and then killed by decapitation. BM chimeric
mice were used, as they do not show the toxic side effects from GCV
treatment seen in LTR-TK transgenic mice, due to a leakiness of TK
expression in nonhemopoietic cells (21). Mice were treated and used in
agreement with institutional guidelines.
mAbs and conjugates
Abs against DC (N418/CD11c, NLDC-145/DEC-205, 53-6.7.2/CD8)
and macrophages (BM8, F4/80, MOMA-1, ER-BMDM1/CD13, M1/70/Mac-1/CD11b)
have been described in more detail elsewhere (22, 23). Abs RA3
6B2/B220/CD45R and KT3/CD3 detect B and T cells, respectively (24, 25).
mAbs were applied as supernatants from hybridoma cultures or as optimal
dilutions after purification (BM8; kindly provided by Biomedicals AG,
Augst, Switzerland). Hybridomas were obtained from the original
producers or American Type Culture Collection (Rockville, MD).
As second-stage reagents we used: anti-rat Ig and anti-hamster Ig conjugated to peroxidase (Jackson ImmunoResearch Laboratories, West Grove, PA), anti-rat Ig and anti-hamster Ig conjugated to FITC (Cappel, Organon Teknika, Turnhout, Belgium and Caltag Laboratories, San Francisco, CA, respectively), and anti-rat Ig conjugated to phycoerythrin (Caltag).
Liposome preparation and in vivo application
Multilamellar liposomes containing clodronate (dichloromethylene bisphosphonate, a gift from Boehringer Mannheim GmbH, Mannheim, Germany) in the aqueous phase or the fluorescent dye DiI (Molecular Probes, Eugene, OR) in the lipid phase were prepared as described previously (26, 27). Liposomes consisted of phosphatidyl choline and cholesterol in 6:1 molar ratio. After washing, the liposomes were resuspended in PBS, and a volume of 0.2 ml, containing about 2 mg of liposome-entrapped clodronate in case of macrophage-depleting liposomes, was injected via the tail vein. After 18 h (DiI-liposomes) or 2 days (clodronate-liposomes), mice were killed and spleens were removed.
Immunohistochemistry
Preparation and staining of cryostat sections for single markers were performed essentially as described before (28). Briefly, 5-µm spleen sections were cut from OCT compound-embedded blocks, air dried, and stored at -20°C until use. After thawing, sections were fixed with p-rosaniline and subsequently incubated with mAb and optimally diluted peroxidase-labeled secondary Ab supplemented with 2% normal mouse serum. Sections were washed between steps with PBS supplemented with 0.05% Tween-20. Ab binding was visualized using NiSO4-supplemented diaminobenzidine as substrate, yielding a black reaction product. Sections were counterstained with nuclear fast red, dehydrated, and embedded in Entellan (Merck, Darmstadt, Germany).
Adaptation for immunohistochemical double labeling was as follows: sections were sequentially incubated with N418 hamster anti-mouse mAb, peroxidase-conjugated anti-hamster Ig, rat anti-mouse mAb, and finally goat anti-rat Ig-alkaline phosphatase (Southern Biotechnology, Birmingham, AL). Alkaline phosphatase activity was visualized first in a 30-min incubation in the dark using naphtol ASMX phosphate (Merck) and Fast Blue BB base (Merck) (final concentration of both, 0.025% in 200 mM Tris-HCl, pH 8.5) as substrate and complexing agent, respectively. Levamisole (0.024%) was added to the reaction mixture to block endogenous alkaline phosphatase activity. After washing the sections in tap water and PBS-Tween, 3-amino-9-ethylcarbazole (0.05% in 100 mM acetate buffer, pH 4.6, supplemented with 0.03% H2O2) was used in a 30-min incubation to detect peroxidase activity. Next, the sections were rinsed with PBS-Tween, embedded in Kaisers Glyceringelatin (Merck), and coverslipped. In these preparations, alkaline phosphatase activity yields a blue reaction product, whereas peroxidase activity appears red.
Spleen cell and DC isolation and culture
Spleens were cut into small pieces and incubated for 1 h at 37°C with 130 U/ml collagenase III (Worthington Biochemical, Freehold, NJ) and 0.1 mg/ml DNase I (Boehringer Mannheim) in RPMI/25 mM HEPES/penicillin/streptomycin (RPMI-HA). We have chosen for this procedure, instead of mechanical disruption in the cold, as it provides a significantly higher yield of splenic DC and macrophages. Control experiments have indicated that DC isolated by either procedure are similar. The resulting digested tissue suspension was teased through a 100-µm filter and centrifuged. Next, erythrocytes were lysed by resuspending the cell pellet in 17 mM Tris-HCl, pH 7.2, containing 144 mM NH4Cl and incubating this for 10 min on ice. Subsequently, the cell suspension was washed with RPMI-HA supplemented with 10% FCS (RPMI-HA-FCS) and resuspended. Part of this suspension was used for flow cytometric analysis and referred to as "fresh total spleen cells." The rest of the cells were cultured overnight at 37°C and 5% CO2 in plastic tissue culture flasks. Next, the nonadherent cells were collected, centrifuged, and resuspended in RPMI-HA-FCS at 1 to 2 x 107 cells per ml (referred to as "overnight total spleen cells"). For DC enrichment, aliquots of 2 ml of this cell suspension were layered on top of 2 ml of Nycodenz (Nycomed Pharma AS, Oslo, Norway) (14.5% in RPMI-HA-FCS) and centrifuged for 20 min at 530 x g. The interface was collected and routinely contained 60 to 80% N418high cells.
Immunofluorescence labeling and flow cytometric analysis
Labeling and subsequent phenotypic analysis of spleen cells by flow cytometry were performed essentially as described before (29). Data were collected using a FACScan (Becton Dickinson, Sunnyvale, CA) and CellQuest software. Resulting data files were further processed for presentation using WinMDI (accessible at http://facs.scripps.edu/).
Conditional elimination of DC in LTR-TK BM chimeric mice
To deplete LTR-TK-expressing DC in BM chimeric mice (see above), these mice received 50 mg of GCV/kg body weight/day using a miniosmotic Alzet pump (Alza Corp., Palo Alto, CA) as described (20). Control mice were sham treated. After 7 days, the mice were killed and spleens were isolated. Efficacy of GCV on LTR-TK transgenic BM was verified by inhibition of granulocyte macrophage-CSF-induced DC generation in BM cultures.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Previously, we have found that the CD13 mAb ER-BMDM1 detects
two major populations of nonlymphocytic cells in mouse spleen: IDC in
the T cell areas and "marginal red pulp macrophages" in patches at
the periphery of the splenic marginal zone (17). To investigate a
possible identity of these marginal red pulp macrophages with the
marginal DC population identified by Agger et al. (10), we labeled
serial spleen sections with ER-BMDM1/CD13 and N418/CD11c. Figure 1
, a and b, shows
that indeed both mAb detect the same populations. Immunohistochemical
double labeling further advanced the notion that ER-BMDM1 and N418
recognize the same DC populations, i.e., both IDC in the T cell zone
and the marginal DC, which are located adjacent to the marginal zone
and extend into the red pulp (data not shown). Also, a minor population
of cells scattered in the red pulp is labeled by both mAb. In contrast,
NLDC-145 only recognizes the population of IDC in the white pulp (Fig. 6c). Double labeling of spleen sections with N418 and
various anti-macrophage mAb indicated that the marginal DC
accumulate at sites where the continuous rim of marginal zone and
metallophilic macrophages is interrupted by the so-called marginal zone
bridging channels (Fig. 2a). These channels,
which are more apparent in rat than in mouse spleen, are also visible
as slight accumulations of T cells and interruptions of the marginal
zone B cell rim (Fig. 2, c and d). Double
labeling with BM8 (Fig. 2b) showed that red pulp
macrophages and marginal DC are essentially distinct populations: only
few N418+ marginal DC show traces of BM8 labeling.
|
|
|
Splenic DC express both DC and macrophage markers
The conclusion reached above, that the previously defined marginal
red pulp macrophages are in fact DC, is in seeming conflict with the
observation, made by immunofluorescence double labeling, that these
cells express multiple markers characteristic of macrophages (17). To
respond to this controversy, we analyzed the phenotype of splenic DC by
flow cytometric double labeling in fresh whole spleen cell suspensions,
after overnight culture, and after subsequent DC enrichment (Fig. 3). DC were identified by N418 labeling.
In accordance with previous reports (30, 31, 32), freshly isolated splenic
DC were found to express high levels of MHC class II, which further
increased during overnight culture. Also, CD13/ER-BMDM1 was uniformly
present on fresh and cultured cells. In contrast, splenic DC showed
heterogeneous labeling for NLDC-145 and CD8: for both markers, only
about 25% of freshly isolated cells was positive. Overnight culture
increased NLDC-145 labeling of both populations, thus retaining their
distinction. Similarly, both populations remained distinct upon culture
with respect to the expression of CD8. These results confirm
previous findings and show that our procedures generate similar
populations to those obtained by others. Remarkably, with regard to
macrophage markers, freshly isolated spleen DC were found to be
uniformly positive for F4/80 and BM8, as well as for Mac-1. Both F4/80
and BM8 expression decreased upon culture, whereas Mac-1 expression was
retained. Taken together, these findings indicate that freshly isolated
splenic DC express markers characteristic of DC as well as macrophage
markers. Upon culture, expression of some of the latter decreases,
whereas expression of some typical DC markers is enhanced.
|
The finding that freshly isolated splenic DC express genuine
macrophage markers raises the question of whether these cells also
display macrophage functions in vivo, especially phagocytosis of
particulate matter. To test this, we injected mice i.v. with liposomes
loaded with clodronate. These liposomes are endocytosed by phagocytic
cells only, and, when applied i.v., eliminate splenic red pulp
macrophages, marginal zone macrophages, and marginal metallophils (27).
Figure 4 confirms that red pulp
macrophages, detected by BM8 labeling, are indeed eliminated 2 days
after liposome application (Fig. 4b). In addition,
marginal zone macrophages and metallophils were depleted (not shown).
Using N418 and ER-BMDM1 to detect DC in these sections, we found that
marginal DC are completely abolished, whereas IDC appear unaffected by
clodronate-liposome treatment (Fig. 4, d and
f). Also, the small population of DC scattered
throughout the red pulp is eliminated by this procedure. These findings
suggest that marginal DC and red pulp DC are eliminated due to
phagocytosis of clodronate-liposomes. Alternatively, the severe
damage caused by depletion of red pulp and marginal zone macrophages
may cause migration of DC. To check this possibility, we i.v. injected
liposomes, now labeled with the fluorescent dye DiI instead of loaded
with clodronate. After approximately 18 h, total spleen cell
suspensions were prepared and analyzed by flow cytometry to identify
cells that had phagocytosed DiI-liposomes. Figure 5 shows that, on average, almost half of
the CD11c+ DC was DiI positive, indicative of their
phagocytosis of liposomes. Interestingly, the intensity of fluorescence
of DC was only three- to fourfold lower compared with that of the
genuine F4/80high macrophages. From these results, we
conclude that splenic marginal DC, in addition to their expression of
macrophage markers, also display actual phagocytic activity in vivo. In
support of this, in a 60-min in vitro phagocytosis assay using
FITC-labeled Listeria, we found that about 30% of
ER-BMDM1+ DC in a freshly isolated spleen cell suspension
were able to internalize bacteria (data not shown). IDC probably are
not phagocytic, as they are not affected in the
clodronate-liposome-treated mice. It should be considered, however,
that the microcirculation in the splenic white pulp allows only limited
access of the IDC to i.v. injected liposomes.
|
|
To delineate further the presumed distinction between the two
splenic DC populations, we asked whether these subsets differed
significantly in turnover. We approached this question in a transgenic
mouse model for conditional DC depletion (20). Previously, in these
LTR-TK transgenic mice, a severe depletion of DC was observed in
various organs after only 7 days of treatment with GCV. Such a brief
depletion time is indicative of a high population turnover, as only
TK-expressing cycling cells are affected by this treatment. In the
current study, we used an improved model, realized by generating
chimeras with LTR-TK transgenic BM (21). From Figure 6
it is evident that
N418+ER-BMDM1+ marginal DC are completely
eliminated by 7-day GCV treatment of LTR-TK chimeras (Fig. 6, a and b). In contrast, the
NLDC-145+ IDC population in these mice is hardly affected
(Fig. 6, c and d). In GCV-treated mice,
red pulp macrophages as well as marginal zone macrophages and marginal
metallophils are still present, thus supporting the selective
elimination of marginal DC on the basis of their expression of TK and
high turnover (data not shown). Thus, from these experiments we
conclude that marginal DC have a significantly higher turnover compared
with IDC.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Our findings on the splenic DC marker profiles confirm and extend
previous reports on splenic DC phenotypes (30, 31, 32, 33). Not only marginal
DC but also IDC, when freshly isolated, express markers thought to be
characteristic of macrophages, such as F4/80, BM8, and Mac-1/CD11b when
Ab binding is assessed by flow cytometry. Using less sensitive
immunohistology, however, a clear distinction can be detected between
the red pulp macrophages, which express high levels of F4/80 and BM8,
and the DC, which express lower levels of these markers. This is in
agreement with previous findings (12). Upon overnight culture, DC
undergo a maturation step and show decreased binding of F4/80 and BM8
mAb, whereas the DC markers, MHC class II and NLDC-145, are
increasingly expressed. With respect to the latter, now cells
originating from the marginal DC population also become
NLDC-145+, but the two populations still are recognized as
separate and discrete. In accordance with recent findings, we observe
CD8 expression by only a subpopulation of DC (3, 31, 32). This
subset corresponds quantitatively to the NLDC-145+
population over a range of frequencies (compare this study with Refs. 3
and 31), and in freshly purified splenic DC it was recently shown that
NLDC-145 and CD8 are expressed by the same cells (32). Based on
this, IDC are the most likely candidates for the CD8+
subset of DC (31, 32), leaving the marginal DC as the
CD8- subset. The latter was indeed confirmed by
immunohistology (our unpublished observations). It cannot be excluded,
however, that some cells with a marginal DC phenotype are located in
the white pulp also under steady-state conditions, as was observed
after LPS administration (34).
Expression of a number of genuine macrophage markers by splenic DC prompted us to investigate the ability of these cells to phagocytose particles as a typical function of macrophages. We have chosen to use relatively large multilamellar phosphatidylcholine liposomes as model particles since numerous previous studies have shown that these agents have a high selectivity for macrophages in vivo and, when loaded with clodronate, can be used for selective elimination of phagocytic cells (27, 35, 36). Based on the actual depletion of marginal DC by clodronate-liposomes and the observed labeling of isolated DC after application of DiI-carrying liposomes, we conclude that at least a subset of DC is phagocytic in vivo. In support of this finding, recent studies in the rat have shown that i.v. applied particulates can be phagocytosed in vivo by DC (16). These cells were detected in hepatic lymph, but the site of actual phagocytosis remained unclear. At least part of the phagocytic DC was suggested to have migrated from the spleen to the liver into hepatic lymph, and in line with this, we propose that the marginal DC are the most likely candidates. Interestingly, migration studies have shown preferential homing of the majority of isolated splenic DC to the liver (37).
The elimination of marginal DC after phagocytosis of clodronate-liposomes occurs in all likelihood by apoptosis of these cells. Recent studies have shown that accumulation of clodronate encapsulated in multilamellar liposomes is a trigger for the apoptotic pathway in activated human monocytes and mouse macrophages (36, 38, 39). Not all cell types, however, that incorporate liposomes seem to die. In vitro application showed that, in addition to monocytes, polymorphonuclear cells and endothelial cells also take up liposomes, but these cells do not undergo apoptosis (39). Elimination is only accomplished in cells 1) in which a sufficiently high threshold of clodronate is reached, and 2) that possess the lysosomal machinery to cleave the liposome membranes and so release their content. These requirements are only met in activated monocytes, macrophages, and macrophage cell lines. Our finding that marginal DC are also depleted by uptake of clodronate-liposomes implies that these cells not only phagocytose at a sufficiently high level, but also possess the required lysosomal activity to break down the liposomes. Thus, in addition to the phenotypic resemblance, these features support the view that the marginal DC are closely related to the macrophage lineage.
The capacity of marginal DC to phagocytose is likely indicative of the
relative immaturity of these cells. In vitro-proliferating BM
progenitors of DC have been shown to phagocytose latex and bacteria,
but lose this capacity upon maturation (15). In addition, the in vivo
phagocytic DC, detected in liver and hepatic lymph after i.v.
application of particulates, are derived from recently divided
precursor cells (16). Furthermore, the mouse precursor DC cell lines
XS52 and FSDC show avid pinocytosis and phagocytosis, which is
suppressed when the cells are stimulated to mature (40, 41). Maturation
of DC is induced by cytokines such as IFN-, IL-1, granulocyte
macrophage-CSF, and TNF, which in vivo are likely produced by T cells
and macrophages, communicating with the immature DC (41, 42, 43). Thus,
phagocytosis by marginal DC, like endocytosis by DC in general, is most
likely an immature trait (13).
Immaturity of the marginal DC is underlined by our finding that these cells are depleted in GCV-treated chimeric LTR-TK mice. Depletion in this system is based upon the termination of elongating DNA by a phosphorylated form of the nucleoside analogue GCV (44). Initial phosphorylation occurs by the Herpes simplex thymidine kinase. Thus, actual depletion is only observed in those cells that synthesize DNA and express the TK transgene, i.e., donor BM-derived DC. So, either the marginal DC themselves or their immediate precursors multiply, while these cells are retained in the marginal location only for a short period of time. Remarkably, IDC were hardly affected in these mice, indicating that these cells have a much slower turnover rate. Such a dichotomy between DC subsets has been suggested before (7), although limited experimental evidence has been provided.
The question then arises whether the "immature" marginal DC are the
precursors of "mature" IDC, as has been suggested (10). Culture of
freshly isolated DC, i.e., primarily marginal DC, indeed induces
expression of NLDC-145 and M342 Ags, typical for IDC (Fig. 3 and Refs.
10 and 32). In addition, isolated splenic DC can home to the white pulp
T cell zones when injected i.v. (45). Furthermore, in vivo
administration of LPS induces maturation of marginal DC, concomitant
with their migration into the T cell areas (34). Some observations,
however, challenge a putative precursor-endstage relationship between
marginal DC and IDC under steady-state conditions. As demonstrated in
our results, a clear phenotypic distinction remains between the two
populations of DC upon culture, despite the induction of NLDC-145 Ag
expression in marginal DC. And, as mentioned before, the majority of
isolated splenic DC homes to the liver, whereas the minority homing to
the splenic T cell areas might represent the population originally
isolated from this location. In addition, CD8 also seems to be a
stable determinant discriminating between the two populations, as it is
present only on IDC. It has been proposed that CD8 is a marker for
DC of lymphoid origin, rather than of myeloid derivation (3, 31, 32).
In contrast, the marginal DC bear all characteristics of a myeloid
origin and close relationship to macrophages, as is apparent from their
elimination by clodronate-liposomes. A different lineage derivation of
marginal DC and IDC, although formally not proven, is clearly
incompatible with a precursor-endstage relationship between these
cells.
Both DC populations seem to play fundamentally distinct roles in the
regulation of T cell responses. CD8+, presumed lymphoid,
DC have recently been shown to kill Ag-specific CD4+ T
cells via Fas-Fas ligand interaction. These cells can stimulate a
prolonged CD8+ T cell response only if exogenous IL-2 is
present (8, 9). In contrast, CD8-, presumed myeloid, DC
are the classic professional initiators of both CD4+ and
CD8+ T cell responses. In this respect, it is an intriguing
notion that the stimulating, myeloid DC are located outside the classic
splenic T cell area, yet are in the migration pathway of homing T
cells, namely in the marginal zone bridging channels (46, 47). In line
with this, activated T cells expressing CD40L have been found in
immunized spleen only near the terminal arteriole, compatible with the
location of the marginal DC, but not in the T cell area of the white
pulp (48). A hypothetical scenario thus might be that circulating T
cells are activated outside the splenic white pulp upon recognition of
cognate Ag presented by myeloid DC, and then move into the
periarteriolar lymphoid sheath, either or not accompanied by the
maturing myeloid DC. In the T cell areas then, the T cell response is
finalized, tightly balanced by the regulatory, lymphoid DC.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Pieter J. M. Leenen, Department of Immunology, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail address:
3 Abbreviations used in this paper: DC, dendritic cell(s); IDC, interdigitating cells; BM, bone marrow; GCV, ganciclovir; LTR, human immunodeficiency virus 1 long terminal repeat; TK, herpes simplex virus type 1 thymidine kinase; LTR-TK mice, HIV1-LTR/HSV1-TK transgenic mice.
Received for publication July 10, 1997. Accepted for publication November 10, 1997.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  M. Bajenoff, N. Glaichenhaus, and R. N. Germain Fibroblastic Reticular Cells Guide T Lymphocyte Entry into and Migration within the Splenic T Cell Zone J. Immunol., September 15, 2008; 181(6): 3947 - 3954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. van Schooten, S. Shahbazi, E. Groot, B. D. Oortwijn, H. M. van den Berg, C. V. Denis, and P. J. Lenting Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo Blood, September 1, 2008; 112(5): 1704 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wynn, P. O. Scumpia, R. D. Winfield, M. J. Delano, K. Kelly-Scumpia, T. Barker, R. Ungaro, O. Levy, and L. L. Moldawer Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists Blood, September 1, 2008; 112(5): 1750 - 1758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dasgupta, J. Bayry, S. Andre, J. D. Dimitrov, S. V. Kaveri, and S. Lacroix-Desmazes Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins J. Immunol., August 1, 2008; 181(3): 1609 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. De Trez, K. Schneider, K. Potter, N. Droin, J. Fulton, P. S. Norris, S.-w. Ha, Y.-X. Fu, T. Murphy, K. M. Murphy, et al. The Inhibitory HVEM-BTLA Pathway Counter Regulates Lymphotoxin Receptor Signaling to Achieve Homeostasis of Dendritic Cells J. Immunol., January 1, 2008; 180(1): 238 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Czeloth, A. Schippers, N. Wagner, W. Muller, B. Kuster, G. Bernhardt, and R. Forster Sphingosine-1 Phosphate Signaling Regulates Positioning of Dendritic Cells within the Spleen J. Immunol., November 1, 2007; 179(9): 5855 - 5863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Louten, N. van Rooijen, and C. A. Biron Type 1 IFN Deficiency in the Absence of Normal Splenic Architecture during Lymphocytic Choriomeningitis Virus Infection. J. Immunol., September 1, 2006; 177(5): 3266 - 3272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. F. H. M. Boonman, L. R. H. M. Schurmans, N. van Rooijen, C. J. M. Melief, R. E. M. Toes, and M. J. Jager Macrophages are vital in spontaneous intraocular tumor eradication. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 2959 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Ciavarra, A. Stephens, S. Nagy, M. Sekellick, and C. Steel Evaluation of Immunological Paradigms in a Virus Model: Are Dendritic Cells Critical for Antiviral Immunity and Viral Clearance? J. Immunol., July 1, 2006; 177(1): 492 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. de Gruijl, C. C. Sombroek, S. M. Lougheed, D. Oosterhoff, J. Buter, A. J. M. van den Eertwegh, R. J. Scheper, and H. M. Pinedo A Postmigrational Switch among Skin-Derived Dendritic Cells to a Macrophage-Like Phenotype Is Predetermined by the Intracutaneous Cytokine Balance. J. Immunol., June 15, 2006; 176(12): 7232 - 7242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Tacke, F. Ginhoux, C. Jakubzick, N. van Rooijen, M. Merad, and G. J. Randolph Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery J. Exp. Med., March 20, 2006; 203(3): 583 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Fogg, C. Sibon, C. Miled, S. Jung, P. Aucouturier, D. R. Littman, A. Cumano, and F. Geissmann A Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells Science, January 6, 2006; 311(5757): 83 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Shao, A. Mednick, M. Alvarez, N. van Rooijen, A. Casadevall, and D. L. Goldman An Innate Immune System Cell Is a Major Determinant of Species-Related Susceptibility Differences to Fungal Pneumonia J. Immunol., September 1, 2005; 175(5): 3244 - 3251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. H. Tan and H. C. O'Neill Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity J. Leukoc. Biol., August 1, 2005; 78(2): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Biburger and G. Tiegs {alpha}-Galactosylceramide-Induced Liver Injury in Mice Is Mediated by TNF-{alpha} but Independent of Kupffer Cells J. Immunol., August 1, 2005; 175(3): 1540 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakamura, F. Ishikawa, K.-h. Sonoda, T. Hisatomi, H. Qiao, J. Yamada, M. Fukata, T. Ishibashi, M. Harada, and S. Kinoshita Characterization and Distribution of Bone Marrow-Derived Cells in Mouse Cornea Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 497 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Oriss, M. Ostroukhova, C. Seguin-Devaux, B. Dixon-McCarthy, D. B. Stolz, S. C. Watkins, B. Pillemer, P. Ray, and A. Ray Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance J. Immunol., January 15, 2005; 174(2): 854 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ato, H. Nakano, T. Kakiuchi, and P. M. Kaye Localization of Marginal Zone Macrophages Is Regulated by C-C Chemokine Ligands 21/19 J. Immunol., October 15, 2004; 173(8): 4815 - 4820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Reid, M. Montoya, P. R. Taylor, P. Borrow, S. Gordon, G. D. Brown, and S. Y. C. Wong Expression of the {beta}-glucan receptor, Dectin-1, on murine leukocytes in situ correlates with its function in pathogen recognition and reveals potential roles in leukocyte interactions J. Leukoc. Biol., July 1, 2004; 76(1): 86 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. O'Neill, H. L. Wilson, B. Quah, J. L. Abbey, G. Despars, and K. Ni Dendritic Cell Development in Long-Term Spleen Stromal Cultures Stem Cells, July 1, 2004; 22(4): 475 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Quah, K. Ni, and H. C. O'Neill In vitro hematopoiesis produces a distinct class of immature dendritic cells from spleen progenitors with limited T cell stimulation capacity Int. Immunol., April 1, 2004; 16(4): 567 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sunderkotter, T. Nikolic, M. J. Dillon, N. van Rooijen, M. Stehling, D. A. Drevets, and P. J. M. Leenen Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response J. Immunol., April 1, 2004; 172(7): 4410 - 4417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matsumoto, H. Inoue, T. Nakano, M. Tsuda, Y. Yoshiura, S. Fukuyama, F. Tsushima, T. Hoshino, H. Aizawa, H. Akiba, et al. B7-DC Regulates Asthmatic Response by an IFN-{gamma}-Dependent Mechanism J. Immunol., February 15, 2004; 172(4): 2530 - 2541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Amprey, G. F. Spath, and S. A. Porcelli Inhibition of CD1 Expression in Human Dendritic Cells during Intracellular Infection with Leishmania donovani Infect. Immun., January 1, 2004; 72(1): 589 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. P. Oliveira, G. M. A. C. Lima, M. T. Shio, P. J. M. Leenen, and I. A. Abrahamsohn Immature macrophages derived from mouse bone marrow produce large amounts of IL-12p40 after LPS stimulation J. Leukoc. Biol., November 1, 2003; 74(5): 857 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Colino and C. M. Snapper Opposing Signals from Pathogen-Associated Molecular Patterns and IL-10 Are Critical for Optimal Dendritic Cell Induction of In Vivo Humoral Immunity to Streptococcus pneumoniae J. Immunol., October 1, 2003; 171(7): 3508 - 3519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Sun, L. Fiette, M. Tanguy, C. Leclerc, and R. Lo-Man Ontogeny and innate properties of neonatal dendritic cells Blood, July 15, 2003; 102(2): 585 - 591. [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]
|
|
|
|
|
|
M. D. Becker, S. R. Planck, S. Crespo, K. Garman, R. J. Fleischman, P. Dullforce, G. W. Seitz, T. M. Martin, D. C. Parker, and J. T. Rosenbaum Immunohistology of Antigen-Presenting Cells In Vivo: A Novel Method for Serial Observation of Fluorescently Labeled Cells Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2004 - 2009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Morelli, A. T. Larregina, W. J. Shufesky, A. F. Zahorchak, A. J. Logar, G. D. Papworth, Z. Wang, S. C. Watkins, L. D. Falo Jr, and A. W. Thomson Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production Blood, January 15, 2003; 101(2): 611 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, W. D. Shlomchik, G. Joe, J.-P. Louboutin, J. Zhu, A. Rivera, D. Giannola, and S. G. Emerson APCs in the Liver and Spleen Recruit Activated Allogeneic CD8+ T Cells to Elicit Hepatic Graft-Versus-Host Disease J. Immunol., December 15, 2002; 169(12): 7111 - 7118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Miller, V. G. Pillarisetty, A. B. Shah, S. Lahrs, Z. Xing, and R. P. DeMatteo Endogenous Granulocyte-Macrophage Colony-Stimulating Factor Overexpression In Vivo Results in the Long-Term Recruitment of a Distinct Dendritic Cell Population with Enhanced Immunostimulatory Function J. Immunol., September 15, 2002; 169(6): 2875 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, L. M. Hillyer, and B. D. Woodward The Capacity of Noninflammatory (Steady-State) Dendritic Cells to Present Antigen in the Primary Response Is Preserved in Acutely Protein- or Energy-Deficient Weanling Mice J. Nutr., September 1, 2002; 132(9): 2748 - 2756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Brissette-Storkus, S. M. Reynolds, A. J. Lepisto, and R. L. Hendricks Identification of a Novel Macrophage Population in the Normal Mouse Corneal Stroma Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2264 - 2271. [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]
|
|
|
|
|
|
Y. Wang, Y. Zhang, H. Yoneyama, N. Onai, T. Sato, and K. Matsushima Identification of CD8alpha +CD11c- lineage phenotype-negative cells in the spleen as committed precursor of CD8alpha + dendritic cells Blood, June 28, 2002; 100(2): 569 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Steptoe, J. M. Ritchie, and L. C. Harrison Increased Generation of Dendritic Cells from Myeloid Progenitors in Autoimmune-Prone Nonobese Diabetic Mice J. Immunol., May 15, 2002; 168(10): 5032 - 5041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Martin, S. R. Ruiz, G. M. del Hoyo, F. Anjuere, H. H. Vargas, M. Lopez-Bravo, and C. Ardavin Dramatic increase in lymph node dendritic cell number during infection by the mouse mammary tumor virus occurs by a CD62L-dependent blood-borne DC recruitment Blood, February 15, 2002; 99(4): 1282 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Jiao, R. Lo-Man, P. Guermonprez, L. Fiette, E. Deriaud, S. Burgaud, B. Gicquel, N. Winter, and C. Leclerc Dendritic Cells Are Host Cells for Mycobacteria In Vivo That Trigger Innate and Acquired Immunity J. Immunol., February 1, 2002; 168(3): 1294 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bozza, R. Gaziano, A. Spreca, A. Bacci, C. Montagnoli, P. di Francesco, and L. Romani Dendritic Cells Transport Conidia and Hyphae of Aspergillus fumigatus from the Airways to the Draining Lymph Nodes and Initiate Disparate Th Responses to the Fungus J. Immunol., February 1, 2002; 168(3): 1362 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. del Hoyo, P. Martin, C. F. Arias, A. R. Marin, and C. Ardavin CD8alpha + dendritic cells originate from the CD8alpha - dendritic cell subset by a maturation process involving CD8alpha , DEC-205, and CD24 up-regulation Blood, February 1, 2002; 99(3): 999 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. O'Connell, W. Li, Z. Wang, S. M. Specht, A. J. Logar, and A. W. Thomson Immature and Mature CD8{alpha}+ Dendritic Cells Prolong the Survival of Vascularized Heart Allografts J. Immunol., January 1, 2002; 168(1): 143 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Colino, Y. Shen, and C. M. Snapper Dendritic Cells Pulsed with Intact Streptococcus pneumoniae Elicit both Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses In Vivo through Distinct Mechanisms J. Exp. Med., December 31, 2001; 195(1): 1 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Byersdorfer and D. D. Chaplin Visualization of Early APC/T Cell Interactions in the Mouse Lung Following Intranasal Challenge J. Immunol., December 15, 2001; 167(12): 6756 - 6764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bonkobara, P. K. Zukas, S. Shikano, S. Nakamura, P. D. Cruz Jr., and K. Ariizumi Epidermal Langerhans Cell-Targeted Gene Expression by a Dectin-2 Promoter J. Immunol., December 15, 2001; 167(12): 6893 - 6900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Burthem, B. Urban, A. Pain, and D. J. Roberts The normal cellular prion protein is strongly expressed by myeloid dendritic cells Blood, December 15, 2001; 98(13): 3733 - 3738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yoshida, H. Kawamoto, S. M. Santee, H. Hashi, K. Honda, S. Nishikawa, C. F. Ware, Y. Katsura, and S.-I. Nishikawa Expression of {alpha}4{beta}7 Integrin Defines a Distinct Pathway of Lymphoid Progenitors Committed to T Cells, Fetal Intestinal Lymphotoxin Producer, NK, and Dendritic Cells J. Immunol., September 1, 2001; 167(5): 2511 - 2521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Kalled, A. H. Cutler, and L. C. Burkly Apoptosis and Altered Dendritic Cell Homeostasis in Lupus Nephritis Are Limited by Anti-CD154 Treatment J. Immunol., August 1, 2001; 167(3): 1740 - 1747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Kirby, U. Yrlid, M. Svensson, and M. J. Wick Differential Involvement of Dendritic Cell Subsets During Acute Salmonella Infection J. Immunol., June 1, 2001; 166(11): 6802 - 6811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Manz, D. Traver, T. Miyamoto, I. L. Weissman, and K. Akashi Dendritic cell potentials of early lymphoid and myeloid progenitors Blood, June 1, 2001; 97(11): 3333 - 3341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. McIlroy, C. Troadec, F. Grassi, A. Samri, B. Barrou, B. Autran, P. Debre, J. Feuillard, and A. Hosmalin Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors Blood, June 1, 2001; 97(11): 3470 - 3477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Grohmann, F. Fallarino, S. Silla, R. Bianchi, M. L. Belladonna, C. Vacca, A. Micheletti, M. C. Fioretti, and P. Puccetti CD40 Ligation Ablates the Tolerogenic Potential of Lymphoid Dendritic Cells J. Immunol., January 1, 2001; 166(1): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Traver, K. Akashi, M. Manz, M. Merad, T. Miyamoto, E. G. Engleman, and I. L. Weissman Development of CD8{alpha}-Positive Dendritic Cells from a Common Myeloid Progenitor Science, December 15, 2000; 290(5499): 2152 - 2154. [Abstract] [Full Text]
|
|
|
|
|
|
A. T. Kamath, J. Pooley, M. A. O'Keeffe, D. Vremec, Y. Zhan, A. M. Lew, A. D'Amico, L. Wu, D. F. Tough, and K. Shortman The Development, Maturation, and Turnover Rate of Mouse Spleen Dendritic Cell Populations J. Immunol., December 15, 2000; 165(12): 6762 - 6770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M.M. den Haan, S. M. Lehar, and M. J. Bevan CD8+ but Not CD8- Dendritic Cells Cross-prime Cytotoxic T Cells In Vivo J. Exp. Med., December 11, 2000; 192(12): 1685 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Gorczynski, K. Yu, and D. Clark Receptor Engagement on Cells Expressing a Ligand for the Tolerance-Inducing Molecule OX2 Induces an Immunoregulatory Population That Inhibits Alloreactivity In Vitro and In Vivo J. Immunol., November 1, 2000; 165(9): 4854 - 4860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Martin, G. M. del Hoyo, F. Anjuere, S. R. Ruiz, C. F. Arias, A. R. Marin, and C. Ardavin Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8alpha - and CD8alpha + dendritic cells are generated from CD4low lymphoid-committed precursors Blood, October 1, 2000; 96(7): 2511 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sato, S. K. Ahuja, M. Quinones, V. Kostecki, R. L. Reddick, P. C. Melby, W. A. Kuziel, and S. S. Ahuja CC Chemokine Receptor (CCR)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-inducing Dendritic Cells: Absence of CCR2 Shifts the Leishmania major-resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation J. Exp. Med., July 10, 2000; 192(2): 205 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Bauman, K. L. Nichols, and J. W. Murphy Dendritic Cells in the Induction of Protective and Nonprotective Anticryptococcal Cell-Mediated Immune Responses J. Immunol., July 1, 2000; 165(1): 158 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. d'Ostiani, G. Del Sero, A. Bacci, C. Montagnoli, A. Spreca, A. Mencacci, P. Ricciardi-Castagnoli, and L. Romani Dendritic Cells Discriminate between Yeasts and Hyphae of the Fungus Candida albicans: Implications for Initiation of T Helper Cell Immunity In Vitro and In Vivo J. Exp. Med., May 8, 2000; 191(10): 1661 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-G. Fischer, U. Bonifas, and G. Reichmann Phenotype and Functions of Brain Dendritic Cells Emerging During Chronic Infection of Mice with Toxoplasma gondii J. Immunol., May 1, 2000; 164(9): 4826 - 4834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Ryman, W. B. Klimstra, K. B. Nguyen, C. A. Biron, and R. E. Johnston Alpha/Beta Interferon Protects Adult Mice from Fatal Sindbis Virus Infection and Is an Important Determinant of Cell and Tissue Tropism J. Virol., April 1, 2000; 74(7): 3366 - 3378. [Abstract] [Full Text]
|
|
|
|
|
|
D. Ashany, A. Savir, N. Bhardwaj, and K. B. Elkon Dendritic Cells Are Resistant to Apoptosis Through the Fas (CD95/APO-1) Pathway J. Immunol., November 15, 1999; 163(10): 5303 - 5311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-G. Fischer and A. K. Bielinsky Antigen presentation function of brain-derived dendriform cells depends on astrocyte help Int. Immunol., August 1, 1999; 11(8): 1265 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. K. Hanson, J. S. Slater, Z. Karabekian, H. W. Virgin IV, C. A. Biron, M. C. Ruzek, N. van Rooijen, R. P. Ciavarra, R. M. Stenberg, and A. E. Campbell Replication of Murine Cytomegalovirus in Differentiated Macrophages as a Determinant of Viral Pathogenesis J. Virol., July 1, 1999; 73(7): 5970 - 5980. [Abstract] [Full Text]
|
|
|
|
|
|
A. Maas, G. M. Dingjan, F. Grosveld, and R. W. Hendriks Early Arrest in B Cell Development in Transgenic Mice That Express the E41K Bruton's Tyrosine Kinase Mutant Under the Control of the CD19 Promoter Region J. Immunol., June 1, 1999; 162(11): 6526 - 6533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Gunn, S. Kyuwa, C. Tam, T. Kakiuchi, A. Matsuzawa, L. T. Williams, and H. Nakano Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization J. Exp. Med., February 1, 1999; 189(3): 451 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gorczynski, Z. Chen, J. Hu, Y. Kai, J. Lei, V. Ramakrishna, and R. M. Gorczynski Evidence That an OX-2-Positive Cell Can Inhibit the Stimulation of Type 1 Cytokine Production by Bone Marrow-Derived B7-1 (and B7-2)-Positive Dendritic Cells J. Immunol., January 15, 1999; 162(2): 774 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Masurier, B. Salomon, N. Guettari, C. Pioche, F. Lachapelle, M. Guigon, and D. Klatzmann Dendritic Cells Route Human Immunodeficiency Virus to Lymph Nodes after Vaginal or Intravenous Administration to Mice J. Virol., October 1, 1998; 72(10): 7822 - 7829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Lambrecht, B. Salomon, D. Klatzmann, and R. A. Pauwels Dendritic Cells Are Required for the Development of Chronic Eosinophilic Airway Inflammation in Response to Inhaled Antigen in Sensitized Mice J. Immunol., April 15, 1998; 160(8): 4090 - 4097. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
