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*
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261; and Departments of
Cell Biology and Physiology, and
Surgery and Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Several reports have indicated that physiologic interactions between hemopoietic cells in the absence of cell death can result in transfer of membrane components between cells. Passive transfer of MHC molecules between allogeneic murine T cell clones has been reported (12), and the internalization by T cells of MHC molecules derived from the surface of APC has been demonstrated (13, 14). DC are highly interactive cells with extensive membrane processes that facilitate cell clustering and interaction with other cells, including T cells and B cells. We reasoned that during such interactions DC might acquire Ag in the absence of apoptosis or necrosis of the donor cell. Ag transfer between live DC has been suggested after the observation that both Ag-naive and Ag-exposed DC are important in T cell proliferation, although transfer was not directly demonstrated (15). Here, we used flow cytometry and live cell imaging techniques to visualize interactions of DC with other cells in a well-characterized monkey model (16). We demonstrate that DC but not macrophages have a remarkable capacity to acquire plasma membrane and intracellular proteins from other live APC and lymphocytes, and that such transfer results in cross-presentation of Ag to MHC class I-restricted CTL.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Immature DC were generated by culturing normal monkey CD14+ monocytes in GM-CSF and IL-4 for 4 days, with an additional 48-h exposure to CD40L (generously provided by Elaine Thomas, Immunex, Seattle, WA) to induce maturation, as described previously (16). Human DC from HLA-typed donors were generated in the same manner. Macrophages were generated by culturing monkey CD14+ monocytes for 24 h in the absence of cytokines. T cells used in the transfer experiments were monocyte-depleted from monkey PBMC and cultured in the presence of 5 µg/ml Con A and 20 U/ml IL-2 for 3 days to generate activated T cells, or for an additional 5 days to generate resting T cells. The EBV-transformed human HLA-A2+ B cell line Croft was generously provided by Olivera Finn (University of Pittsburgh, Pittsburgh, PA). The oligoclonal T cell line TIL620, which recognizes two epitopes of the melanoma Ag gp100 (17), was derived in the laboratory of Dr. Steven Rosenberg (National Institutes of Health, Bethesda, MD).
Fluorescence labeling
Cells were incubated with the lipophilic probe 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodi-carbocyanine perchlorate (DiD; excitation/emission spectra = 644 nm/663 nm) as described (18) and the thiol-reactive chloromethyl probe 5-chloromethylfluorescein diacetate (CMFDA; 492 nm/516 nm; both from Molecular Probes, Eugene, OR) at a concentration of 0.5µg/ml in 5 mM EDTA for 30 min at 37°C. Any dead cells were removed by centrifugation through sodium diatrizoate and Ficoll (Sigma, St. Louis, MO).
Transfer assays and flow cytometric analysis
Unlabeled DC, macrophages, B cells, or T cells with or without pretreatment with 10 µg/ml cytochalasin D were cocultured with labeled DC at various ratios at 4 or 37°C in 24- or 48-well plates at a concentration of 1 x 105 cells/ml. For transwell studies, labeled DC were added to 0.4-µm pore transwell chambers (Millipore, Bedford, MA) inserted into wells containing unlabeled DC. Cells were harvested at various intervals and maintained on ice until analyzed on a FACSCaliber flow cytometer (Becton Dickinson, Mountain View, CA) by using CellQuest software (Becton Dickinson). All analyses were done by using log10 fluorescence. In some experiments, cells were fixed in 2% paraformaldehyde before analysis by flow cytometry. We determined in preliminary studies that fixation did not lead to leakage of dye from DiD- and CMFDA-labeled cells (data not shown).
Detection of apoptosis
DC were labeled with DiD and incubated with unlabeled DC for various time periods. Apoptosis was measured by using the TUNEL assay (Boehringer Mannheim, Indianapolis, IN) and staining with Alexa Fluor 488 annexin V (Molecular Probes) as per manufacturer’s instructions. As a positive control for apoptosis, T cells were treated with a UVB light source calibrated at 0.6 mJ/cm2/sec for 8 min and analyzed 12–16 h later.
Live cell microscopy
DC labeled with DiD were introduced into a Bioptechs FCS2 (Butler, PA) closed microscope chamber maintained at 37°C and allowed to adhere. CMFDA-labeled DC were then added in medium containing Hoescht 33342 to label nuclei. Cells were imaged with a Zeiss Axiovert 135 microscope (Oberkochen, Germany) equipped with an XYZ stage, dual excitation filter wheels (Ludl, Hawthorne, NY), shuttered xenon and halogen light sources, and an Orca 12-bit cooled charge-coupled device camera (Hamamatsu, Tokyo, Japan). Images from five random fields were collected every 4 min for each of the illumination conditions with Metamorph software (Universal Imaging, West Chester, PA). The time-lapse sequences were integrated into movies and observed. Cell-cell interactions were tagged and tracked by particle tracking methods within the Metamorph software.
Generation of recombinant adenovirus and transduction of DC
Recombinant adenovirus encoding gp100 (Ad-gp100) was generated
by cloning a SalI-NotI fragment containing
full-length human gp100 (generously provided by Dr. Stephan Wagner,
University of Essen, Essen, Germany) into the pAdlox shuttle vector,
with subsequent cotransfection with 
5 helper virus into the CRE8
packaging cell line as described previously (19). DC or
macrophages were transduced with Ad-gp100 at a multiplicity of
infection of 100 by adding virus directly to cells in culture as
described (16). Cells were washed extensively at 24 h
after infection to remove free virus and cultured for an
additional 24–36 h to allow for protein expression. We routinely
achieve 90% transduction efficiency using this method
(16).
IFN-
enzyme-linked immunospot (ELISPOT) assay
TIL620 cells (3 x 104) were cultured
with the same number of Ad-gp100-transduced immature monkey DC or
macrophages with and without immature human DC or macrophages on
Multiscreen-HA plates (Millipore) coated with anti-human IFN- Ab
(1-D1K; MABTECH, Stockholm, Sweden). After 18 h of incubation,
IFN- production was detected by labeling with a second
anti-human IFN- Ab (7-B6-1; MABTECH) as described previously
(19). Spots were enumerated by using a dissecting
microscope.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Our initial studies focused on interactions between immature DC,
as these cells are actively phagocytic and function in Ag capture
(16, 20). DC were dual-labeled with DiD and CMFDA to track
movement of plasma membrane and intracellular proteins, respectively,
and cocultured with unlabeled cells for various time periods before
flow cytometric analysis. To establish the validity of the fluorescence
transfer system, we did a number of control experiments. When labeled
DC were cultured for 4 h with unlabeled DC pretreated with
cytochalasin D, an inhibitor of membrane ruffling, transfer of
fluorescence was substantially inhibited. Similarly, unlabeled and
labeled DC populations remained separate when cultured for 4 h at
4°C (Fig. 1
a). In addition,
coculture of labeled DC with resting T cells for 4 h at 37°C did
not result in fluorescence transfer between cell populations (Fig. 1a). These experiments indicate that fluorescent labels
remain cell associated and do not passively transfer between cells. In
contrast to the control experiments, when labeled and unlabeled DC were
cultured together at 37°C in the absence of phagocytic inhibitors
transfer of DiD-labeled plasma membrane occurred rapidly, as by 1
h of coculture, 52% of unlabeled cells were
DID+, and by 4 h, up to 95% were
DiD+ (Fig. 1b). Transfer of CMFDA
occurred in cells that were DiDbright, indicating
that movement of plasma membrane was accompanied by movement of
cytoplasmic protein to unlabeled DC. Labeled DC were viable at all time
points of the experiment as measured by lack of staining using both the
TUNEL assay and annexin V binding (Fig. 1b), indicating that
transfer of membrane and cytoplasmic proteins between cells was not the
result of uptake of apoptotic material.
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a). This indicates that
direct cell-cell contact is required and reinforces the earlier finding
that passive movement of dye does not contribute to transfer of
fluorescence between cells. In addition, by using different ratios of
labeled and unlabeled DC, we demonstrate that transfer of plasma
membrane and intracellular proteins between DC is an extremely
efficient process, as 43% of unlabeled DC acquired fluorescence within
4 h when mixed with labeled DC at a 4:1 ratio (Fig. 2b). Together, these data indicate that DC can readily
transfer plasma membrane and, to a lesser extent, cytoplasmic proteins
to other live DC.
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To determine whether the capacity to acquire labeled plasma
membrane and intracellular proteins from live cells was unique to
immature DC, we performed similar studies with different DC populations
as well as macrophages, which are highly effective at acquiring
cellular Ag via uptake of apoptotic material (4). We first
compared immature DC with DC that had been treated with CD40L to induce
maturation, which is known to down-regulate phagocytic function
(16, 21). Immature DC were able to acquire plasma membrane
and intracellular labels with similar efficiency irrespective of the
maturation state of the labeled population. When DC were matured with
CD40L, the capacity to acquire labeled membrane and intracellular
proteins from either immature or mature DC was suppressed by 
50%,
indicating that acquisition was primarily a function of immature DC
(Fig. 3a). The process of
transfer did not result in maturation of DC, as coculture of unlabeled
immature DC with DiD- and CMFDA-labeled DC for 6 h did not result
up-regulation of CD86 or expression of the maturation marker CD83 (data
not shown). Expression of CD83 is induced on immature DC after exposure
to CD40L for the same time period (data not shown). In contrast to DC,
macrophages were extremely limited in the capacity to acquire labeled
plasma membrane and intracellular proteins from either live macrophages
or immature DC (Fig. 3b). Conversely, immature DC readily
acquired Ag from labeled macrophages (Fig. 3b).
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c). Similar findings were generated when
immature DC were cultured with labeled resting monkey T cells, the
Jurkat T cell line, and the 174XCEM.T1 T-B cell hybrid (data not
shown). These experiments indicate that DC are unique in the capacity
to acquire cellular components from other APC and from lymphocytes. Direct visualization of plasma membrane transfer between live DC
To study the dynamics of transfer between individual DC, we used
live cell fluorescence microscopy, which allows real-time imaging of
cellular interactions in culture. DC labeled with DiD were seeded into
the microscope chamber and an equal number of CMFDA-labeled DC then
were added (Fig. 4, 0 min). Detection of
double-labeled cells over time signaled transfer of cellular components
between cells. DC were highly motile and frequently moved in and out of
small clusters, while rapidly extending and retracting plasma membrane
processes (see supplemental video at www.sbic.pitt.edu/harshyne/figure 4). During some of these interactions, large portions of DiD-labeled
plasma membrane were physically pulled from one DC to another (Fig. 4, 48–168 min). Transferred membrane appeared to be contained in
endocytic vesicles of up to 1 µm in diameter, and frequently multiple
vesicles were present within single DC (Fig. 4, 192–216 min). DC that
had acquired membrane could be seen in isolation as double-labeled
cells less than 4 h after the initiation of the experiment (Fig. 4, 216 min). Importantly, DC that had donated membrane also moved away
and interacted with other DC, indicating continued viability of these
cells (Fig. 4, 192–216 min). To definitively rule out the
contribution of apoptotic cell death in transfer of fluorescent label
between DC, we used Hoescht 33342 to label nuclei during live cell
imaging. Nuclei of cells remained intact and noncondensed during all
stages of cell interaction and transfer, as highlighted by the images
collected at 0, 96, and 216 min (Fig. 5).
These data provide direct evidence that DC involved in plasma membrane
transfer were viable.
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To ascertain the immunological significance of the observed
transfer between DC, we developed a xenogeneic T cell stimulation assay
with TIL620, an HLA-A2-restricted CTL line specific for melanoma Ag
gp100 (17). Ad-gp100 was used to express gp100 protein as
an endogenous cytoplasmic Ag in DC. Immature monkey DC, confirmed to be
HLA-A2- by Ab staining (data not shown), were
transduced with Ad-gp100 and cocultured in equal numbers with immature
HLA-A2+ human DC. TIL620 cells were added to the
culture and IFN- production was assayed 18 h later by using
ELISPOT. As expected, culturing Ad-gp100 transduced
HLA-A2+ DC with TIL620 resulted in vigorous
IFN- release (Fig. 6a).
However, coculture of Ad-gp100 transduced monkey DC with
HLA-A2+ human DC was also effective at inducing
cytokine release from TIL620 (Fig. 6a). Cytokine production
was not attributable to direct stimulation of TIL620 by transduced
monkey DC, as coculture with HLA-A2- human DC
did not elicit significant IFN- production. Similarly, coculture of
monkey DC and HLA-A2+ human DC in the absence of
gp100 resulted in negligible stimulation of TIL620 (Fig. 6a). When HLA-A2+ macrophages were
used as acceptor cells with Ad-gp100-transduced monkey DC minimal
IFN- release by TIL620 was observed (Fig. 6b), consistent
with the flow cytometry data indicating that macrophages cannot acquire
plasma membrane or intracellular protein from live cells. Directly
transduced HLA-A2+ macrophages efficiently
stimulated TIL620 (Fig. 6b).
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c). Apoptosis of human DC
directly transfected with Ad-gp100 did occur after 18 h of
coincubation with TIL620 (Fig. 6c). In summary, the ELISPOT
data are consistent with direct transfer of intracellular Ag between
live DC resulting in processing and presentation in MHC class
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Several findings provide conclusive evidence that transfer occurred independently of apoptosis, the common mechanism cited for acquisition of cellular Ag by DC (2, 3). First, labeled DC used in the 4 h coculture experiments had intact DNA as measured by TUNEL assay. Importantly, DC did not undergo apoptosis during the assays as measured by annexin V staining, which detects the early apoptotic event of phosphatidylserine membrane translocation. Second, live cell imaging experiments clearly demonstrated that DC maintained intact nuclear structure, cell morphology, and motility before, during, and after transfer of fluorescent label to other DC. Third, gp100-transduced monkey DC were TUNELneg for the duration of the 18-h ELISPOT assay, indicating that apoptosis of these cells did not contribute to Ag acquisition by human DC with subsequent stimulation of T cells. TIL620 were clearly capable of killing Ag-bearing DC as evidenced by apoptosis in gp100-transduced HLA-A2+ DC. We hypothesize that apoptosis would become apparent in HLA-A2+ DC cocultured with gp100-transduced monkey DC had a longer time period elapsed to allow for sufficient Ag transfer and processing in recipient DC. Finally and most notably, macrophages did not acquire fluorescently labeled membrane and cytoplasm from DC and other macrophages, nor did they cross-present Ag when cocultured with live Ag-expressing DC, despite the exquisite capacity of these cells to phagocytose apoptotic material (4). This finding highlights an apparent distinction between DC and macrophages in that both cell types internalize particulate material, but only DC are able to acquire significant levels of Ag from other live cells.
The observed mechanism of Ag acquisition by DC also appears to be independent of exosomes, which are 50- to 90-nm diameter vesicles released from DC and other cells that have been shown to function as Ag-presenting moieties (22, 23). Studies using DC pulsed with FITC have suggested a role for secreted exosomes in uptake by other DC, although Ag transfer was more effective after direct cell contact (15). In our experiments, acquisition of fluorescently labeled membrane and cytoplasm was completely abrogated by a 0.4-µm transwell filter, a pore size that would not restrict flow of exosomes. The live cell microscopy images revealed that intimate DC-DC contact resulted in physical stripping of membrane from one cell by another, leading to the formation of relatively large vesicles up to 1 µm in diameter. DC appeared to interact via plasma membrane extensions, suggesting that these characteristic cell processes play an important role in Ag transfer between DC. Hence, DC can secrete small exosomes into the supernatant but have the capacity to readily produce substantially larger vesicles after direct interaction with other DC.
The functional studies indicated that endogenous tumor Ag expressed in one DC could be acquired by another DC for cross-presentation to class I-restricted CTL. Cross-presentation by DC of cell-associated Ag in MHC class I previously only had been demonstrated for Ag derived from dead or dying cells (2, 3, 4, 5, 6, 7, 8). In our studies, it is likely that cytoplasmic Ag was carried within vesicles that were observed being transferred between DC by live-cell imaging. This is consistent with the flow cytometry data showing that cells that had acquired substantial membrane label also acquire labeled intracellular proteins. Whether Ag is transferred intact and requires further processing in the recipient DC before loading on MHC class I molecules is not known. An alternative mechanism for cross-presentation could be trafficking of plasma membrane containing MHC molecules in a reverse direction, supported by recent findings that T cells can acquire MHC-peptide complexes from APC after TCR engagement (13, 14). However, transferred HLA-A2 would have to be internalized by the monkey DC, loaded with processed gp100 Ag, and trafficked intact to the cell surface for subsequent recognition by TIL620. We currently are investigating the precise mechanism of cross-presentation and whether reciprocal transfer of Ag and MHC molecules occurs in this system.
The marked degree of Ag transfer detected in this study suggests that
Ag acquisition by DC from other viable cells may be an important
process in vivo. Acquisition of Ag was significantly more efficient by
immature than mature DC, indicating that Ag transfer in vivo may occur
at the level of the skin and other peripheral tissues where immature DC
reside. Hence, DC directly infected with a pathogen could provide a
continuous source of Ag for resident Langerhan’s cells or immature DC
recruited to the site through release of inflammatory cytokines
(24), thereby rapidly and effectively amplifying the
immune response. Transfer of Ag between DC in skin would enable
subpopulations that are apparently nonmigratory to nevertheless
stimulate robust CTL responses in vivo, as has been suggested for
CD8
+ lymphoid DC in the mouse
(25). This may be the case for mature DC administered as
vaccines, which we have shown in the primate model have a tendency to
remain at the site of injection (16). Alternatively, Ag
transfer could occur after migration of Ag-exposed DC to lymph nodes as
has been suggested by others (11), mediated by lymph node
DC subpopulations that have Ag-acquiring capacity (26).
Moreover, our data indicate that cells other than DC can serve as Ag
donors, including macrophages, T cells, and B cells. Hence, macrophages
containing phagocytosed material could serve as a source of Ag for DC
in peripheral tissues. Similarly, lymphocytes or macrophages infected
with pathogens could donate Ag to DC. This latter scenario suggests a
mechanism whereby DC could acquire Ag derived from pathogens that
preferentially infect macrophages and lymphocytes without necessarily
causing cell death, such as HIV and EBV.
It is believed that maturation is required for DC to become efficient stimulators of Ag-specific T cells (6, 27). Studies indicate that uptake of apoptotic material by itself may not provide sufficient stimulus for maturation of DC and that additional stimuli provided by necrotic cells may be required for effective Ag presentation (7). In addition, uptake of apoptotic material by DC that have migrated from the gut has been reported, suggesting that DC exposed to Ag in this manner may serve to induce T cell tolerance to intestinal Ag in draining lymph nodes (28). However, in our studies, immature DC readily acquired Ag from other immature DC and were able to cross-present Ag to CTL, suggesting that maturation signals may not be essential for effective immunostimulatory function. It remains to be determined whether Ag transfer between live DC is involved in induction of tolerance to self.
In summary, our studies reveal that interactions between DC and other healthy cells result in acquisition of membrane and cytoplasmic components by the DC, and subsequent cross-presentation to T cells. We suggest that this previously unrecognized means of Ag transfer might be important in the development and regulation of immune responses in vivo.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Simon M. Barratt-Boyes, Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261.
3 Abbreviations used in this paper: DC, dendritic cells; DiD, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodi-carbocyanine perchlorate; CMFDA, 5-chloromethylfluorescein diacetate; Ad-gp100, recombinant adenovirus expressing gp100; ELISPOT, enzyme-linked immunospot assay.
Received for publication August 31, 2000. Accepted for publication January 8, 2001.
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3 integrin and requires intracellular and extracellular calcium. Eur. J. Immunol. 27:1893.[Medline]
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C.-H. Wei, R. Trenney, M. Sanchez-Alavez, K. Marquardt, D. L. Woodland, S. J. Henriksen, and L. A. Sherman Tissue-Resident Memory CD8+ T Cells Can Be Deleted by Soluble, but Not Cross-Presented Antigen J. Immunol., November 15, 2005; 175(10): 6615 - 6623. [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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P. Correale*, M. G. Cusi, M. T. Del Vecchio, A. Aquino, S. Prete, K. Y. Tsang, L. Micheli, C. Nencini, M. La Placa*, F. Montagnani*, et al. Dendritic Cell-Mediated Cross-Presentation of Antigens Derived from Colon Carcinoma Cells Exposed to a Highly Cytotoxic Multidrug Regimen with Gemcitabine, Oxaliplatin, 5-Fluorouracil, and Leucovorin, Elicits a Powerful Human Antigen-Specific CTL Response with Antitumor Activity in Vitro J. Immunol., July 15, 2005; 175(2): 820 - 828. [Abstract] [Full Text] [PDF]
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S. B. J. Wong and R. F. Siliciano Contribution of Virus-Like Particles to the Immunogenicity of Human Immunodeficiency Virus Type 1 Gag-Derived Vaccines in Mice J. Virol., February 1, 2005; 79(3): 1701 - 1712. [Abstract] [Full Text] [PDF]
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G. Driessens, M. Hamdane, V. Cool, T. Velu, and C. Bruyns Highly Successful Therapeutic Vaccinations Combining Dendritic Cells and Tumor Cells Secreting Granulocyte Macrophage Colony-stimulating Factor Cancer Res., November 15, 2004; 64(22): 8435 - 8442. [Abstract] [Full Text] [PDF]
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A. E. Morelli, A. T. Larregina, W. J. Shufesky, M. L. G. Sullivan, D. B. Stolz, G. D. Papworth, A. F. Zahorchak, A. J. Logar, Z. Wang, S. C. Watkins, et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells Blood, November 15, 2004; 104(10): 3257 - 3266. [Abstract] [Full Text] [PDF]
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J. Janda, P. Schoneberger, M. Skoberne, M. Messerle, H. Russmann, and G. Geginat Cross-Presentation of Listeria-Derived CD8 T Cell Epitopes Requires Unstable Bacterial Translation Products J. Immunol., November 1, 2004; 173(9): 5644 - 5651. [Abstract] [Full Text] [PDF]
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A. M. Gallegos and M. J. Bevan Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation J. Exp. Med., October 18, 2004; 200(8): 1039 - 1049. [Abstract] [Full Text] [PDF]
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O. B. Herrera, D. Golshayan, R. Tibbott, F. S. Ochoa, M. J. James, F. M. Marelli-Berg, and R. I. Lechler A Novel Pathway of Alloantigen Presentation by Dendritic Cells J. Immunol., October 15, 2004; 173(8): 4828 - 4837. [Abstract] [Full Text] [PDF]
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C. Maranon, J.-F. Desoutter, G. Hoeffel, W. Cohen, D. Hanau, and A. Hosmalin Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes PNAS, April 20, 2004; 101(16): 6092 - 6097. [Abstract] [Full Text] [PDF]
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G. Yang, J. Addai, W.-h. Tian, A. Frolov, T. M. Wheeler, and T. C. Thompson Reduced Infiltration of Class A Scavenger Receptor Positive Antigen-Presenting Cells Is Associated with Prostate Cancer Progression Cancer Res., March 15, 2004; 64(6): 2076 - 2082. [Abstract] [Full Text] [PDF]
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L. Shen and K. L. Rock Cellular protein is the source of cross-priming antigen in vivo PNAS, March 2, 2004; 101(9): 3035 - 3040. [Abstract] [Full Text] [PDF]
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F. Andre, N. Chaput, N. E. C. Schartz, C. Flament, N. Aubert, J. Bernard, F. Lemonnier, G. Raposo, B. Escudier, D.-H. Hsu, et al. Exosomes as Potent Cell-Free Peptide-Based Vaccine. I. Dendritic Cell-Derived Exosomes Transfer Functional MHC Class I/Peptide Complexes to Dendritic Cells J. Immunol., February 15, 2004; 172(4): 2126 - 2136. [Abstract] [Full Text] [PDF]
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R. Sporri and C. Reis e Sousa Newly Activated T Cells Promote Maturation of Bystander Dendritic Cells but Not IL-12 Production J. Immunol., December 15, 2003; 171(12): 6406 - 6413. [Abstract] [Full Text] [PDF]
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K. Brown, W. Gao, S. Alber, A. Trichel, M. Murphey-Corb, S. C. Watkins, A. Gambotto, and S. M. Barratt-Boyes Adenovirus-Transduced Dendritic Cells Injected into Skin or Lymph Node Prime Potent Simian Immunodeficiency Virus-Specific T Cell Immunity in Monkeys J. Immunol., December 15, 2003; 171(12): 6875 - 6882. [Abstract] [Full Text] [PDF]
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P. Kleindienst and T. Brocker Endogenous Dendritic Cells Are Required for Amplification of T Cell Responses Induced by Dendritic Cell Vaccines In Vivo J. Immunol., March 15, 2003; 170(6): 2817 - 2823. [Abstract] [Full Text] [PDF]
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L. A. Harshyne, M. I. Zimmer, S. C. Watkins, and S. M. Barratt-Boyes A Role for Class A Scavenger Receptor in Dendritic Cell Nibbling from Live Cells J. Immunol., March 1, 2003; 170(5): 2302 - 2309. [Abstract] [Full Text] [PDF]
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E. Mougneau, S. Hugues, and N. Glaichenhaus Antigen Presentation by Dendritic Cells In Vivo J. Exp. Med., October 21, 2002; 196(8): 1013 - 1016. [Full Text] [PDF]
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Y. Tada, J. O-Wang, Y. Takiguchi, K. Tatsumi, T. Kuriyama, S. Okada, T. Tokuhisa, S. Sakiyama, and M. Tagawa Cutting Edge: A Novel Role for Fas Ligand in Facilitating Antigen Acquisition by Dendritic Cells J. Immunol., September 1, 2002; 169(5): 2241 - 2245. [Abstract] [Full Text] [PDF]
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 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]
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 E. B. Olasz, J. Linton, and S. I. Katz Soluble proteins and haptens on bone marrow-derived dendritic cells are presented to host CD4 T cells in an MHC-restricted manner Int. Immunol., May 1, 2002; 14(5): 493 - 502. [Abstract] [Full Text] [PDF]
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Y. Valdez, W. Mah, M. M. Winslow, L. Xu, P. Ling, and S. E. Townsend Major Histocompatibility Complex Class II Presentation of Cell-associated Antigen Is Mediated by CD8{alpha}+ Dendritic Cells In Vivo J. Exp. Med., March 11, 2002; 195(6): 683 - 694. [Abstract] [Full Text] [PDF]
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S. Koido, Y. Tanaka, D. Chen, D. Kufe, and J. Gong The Kinetics of In Vivo Priming of CD4 and CD8 T Cells by Dendritic/Tumor Fusion Cells in MUC1-Transgenic Mice J. Immunol., March 1, 2002; 168(5): 2111 - 2117. [Abstract] [Full Text] [PDF]
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X.-Q. Zhao, X.-L. Huang, P. Gupta, L. Borowski, Z. Fan, S. C. Watkins, E. K. Thomas, and C. R. Rinaldo Jr. Induction of Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ and CD4+ T-Cell Reactivity by Dendritic Cells Loaded with HIV-1 X4-Infected Apoptotic Cells J. Virol., February 22, 2002; 76(6): 3007 - 3014. [Abstract] [Full Text] [PDF]
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G. Arrode, C. Boccaccio, J.-P. Abastado, and C. Davrinche Cross-Presentation of Human Cytomegalovirus pp65 (UL83) to CD8+ T Cells Is Regulated by Virus-Induced, Soluble-Mediator-Dependent Maturation of Dendritic Cells J. Virol., January 1, 2002; 76(1): 142 - 150. [Abstract] [Full Text] [PDF]
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 M. F. Lipscomb and B. J. Masten Dendritic Cells: Immune Regulators in Health and Disease Physiol Rev, January 1, 2002; 82(1): 97 - 130. [Abstract] [Full Text] [PDF]
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R. Kammerer, D. Stober, P. Riedl, C. Oehninger, R. Schirmbeck, and J. Reimann Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells J. Immunol., January 1, 2002; 168(1): 108 - 117. [Abstract] [Full Text] [PDF]
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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]
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L) or unlabeled macrophages (M
