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Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2484-2490
FOCUS ON HEMATOLOGY
From the Division of Clinical Research, Fred Hutchinson Cancer
Research Center, Hematologics, Inc, and the Department of Medicine,
Division of Oncology, University of Washington, Seattle, WA.
Peripheral blood stem cells (PBSC) obtained from
granulocyte-colony stimulating factor (G-CSF)-mobilized donors are
increasingly used for allogeneic transplantation. Despite a 10-fold
higher dose of transplanted T cells, acute graft-versus-host disease (GVHD) does not develop in higher proportion in recipients of PBSC than
in recipients of marrow. T cells from G-CSF-treated experimental
animals preferentially produce IL-4 and IL-10, cytokines characteristic
of Th2 responses, which are associated with diminished GVHD-inducing
ability. We hypothesized that G-CSF-mobilized PBSC contain
antigen-presenting cells, which prime T-lymphocytes to produce Th2 cytokines. Two distinct lineages of dendritic cells (DC)
have been described in humans, DC1 and DC2, according to their ability
to induce naive T-cell differentiation to Th1 and Th2 effector cells,
respectively. We have used multicolor microfluorometry to enumerate DC1
and DC2 in the peripheral blood of normal donors. G-CSF treatment with
10 to 16 µg/kg per day for 5 days increased peripheral blood DC2
counts from a median of 4.9 × 106/L to 24.8 × 106/L (P = .0009), whereas DC1 counts did not
change. Purified DC1, from either untreated or G-CSF treated donors,
induced the proliferation of allogeneic naive T cells, but
fresh DC2 were poor stimulators. Tumor necrosis factor-
Granulocyte-colony stimulating factor (G-CSF) has been
used in the clinic for its ability to mobilize hematopoietic stem cells from the bone marrow into the bloodstream of patients or normal donors.1,2 Administration of G-CSF followed by
leukapheresis allows the harvest of a sufficient number of stem cells
to engraft autologous or allogeneic recipients.3-7 Clinical
data and results in experimental animals indicate that allografts from
G-CSF-treated donors have peculiar immunologic features. In humans,
G-CSF-mobilized peripheral blood stem cell (PBSC) grafts do not cause a
higher incidence of acute graft-versus-host disease (GVHD) than marrow grafts, despite at least a 10-fold higher T-cell dose,1 and they achieve better engraftment across human leukocyte antigen (HLA) barriers.8,9 PBSC grafts, however,
may be associated with an increased incidence of chronic
GVHD.10,11
T cells from blood or spleen cells of G-CSF-treated mice show decreased
ability to induce GVHD in allogeneic recipients, presumably because of
their polarization toward T helper 2 (Th2) cells, which produce the
cytokines interleukin-4 (IL-4) and IL-10.12,13 In nature,
Th2 cells are involved in allergic responses dominated by the B-cell
production of IgE and the recruitment of eosinophils and
basophils.14 In contrast, Th1 cells produce interferon
(IFN)- Dendritic cells (DC) are the only antigen-presenting cells that can
prime naive T cells to a new antigen.18 Two
distinct lineages of DC have been described in humans. Myeloid DC (or
DC1) express myeloid antigens CD11c, CD13, and CD33, originate from myeloid bone marrow precursors, and require the presence of GM-CSF for
their survival.19-23 In human peripheral blood, DC1 are
identified as negative for lymphoid and myeloid cell-specific markers
(lin In the current study, we demonstrate that G-CSF treatment selectively
increases the number of DC2 in the peripheral blood, so that PBSC used
for allogeneic transplantation contain more DC2 than marrow but a
similar number of DC1.
Cell samples
Monoclonal antibodies
Flow microfluorometry Cells were stained without further separation to minimize selective loss. Erythrocytes were lysed after staining, using FACS Lysing Solution (Becton Dickinson) according to the manufacturer's instructions. Dendritic cells were identified as positive for anti-HLA-DR peridin chlorophyll protein (PerCP)-conjugated and negative for a mixture of FITC-conjugated mAbs specific for lineage markers on T cells (CD3), B cells (CD19, CD20, surface IgM), natural killer cells (CD16, CD56), monocytes (CD14), neutrophils (CD16), and progenitor cells (CD34). Anti-CD11c PE or IL-3R PE were used for identification
of DC1 and DC2 subpopulations, respectively. Selected samples were
stained with CD4 PE or CD11c PE, and with CD11c APC or IL-3R biotin
plus streptavidin allophycocyanin-conjugated. Three-color analysis was performed using a FACScan (Becton Dickinson), and 4 color-analysis was performed using a FACSCalibur flow cytometer (Becton Dickinson). The number of total white blood cells (WBC) in the
samples was determined using a NE8000 Sysmex (TOA, Kobe, Japan) automated cell counter. The absolute number of
DC1 and DC2 was calculated from the WBC count multiplied by the
proportion of each subpopulation among the WBC, as determined by flow
cytometric analysis.
DC separation for functional assays PBMC from normal or G-CSF treated donors were isolated by Ficoll-Hypaque density gradient centrifugation at 800g for 25 minutes, then washed twice in phosphate-buffered saline. PBMC were then depleted of CD14+ monocytes and CD19+ B cells by labeling with anti-CD14 and anti-CD19 magnetic microbeads (Miltenyi-Biotec, Bergisch Gladbach, Germany) and depleting the labeled cells on a high-gradient magnetic separation column (VarioMACS; Miltenyi-Biotec). Recovered cells were labeled with anti-HLA-DR magnetic microbeads (Miltenyi-Biotec), then positively selected on a magnetic separation column (MidiMACS; Miltenyi-Biotec). The immunomagnetic purification was performed according to the manufacturer's instructions. The entire procedure lasted 4 to 6 hours, during which cells were kept at 4°C. Aliquots of enriched cells were checked for purity and were consistently more than 96% HLA-DR+. Cells were then stained with FITC lineage markers, CD11c PE, and IL-3R biotin plus streptavidin TC, then sorted on a
FACS Vantage (Becton Dickinson). Aliquots of sorted cells were
reanalyzed for their purity, which was consistently greater than 95%
for DC1 and greater than 98% for DC2. Cross-contamination of each DC
subset with cells belonging to the other subset was consistently below
the detection limit of the assay.
T-cell separation CD4+CD45RA+ naive T cells were purified by using the CD4 MACS Multisort Kit (Miltenyi-Biotec) according to the manufacturer's instructions. Briefly, Ficoll-separated mononuclear cells were first labeled with anti-CD4 magnetic microbeads and positively selected on a magnetic separation column. Then the microbeads were enzymatically removed from the antibody by using MACS release reagent (Miltenyi-Biotec). CD4+ cells were then labeled with anti-CD45RA microbeads (Miltenyi-Biotec) and positively selected on a magnetic separation column. Aliquots of sorted naive T cells were restained with anti-CD4 FITC and anti-D45RA PE, and their purity was consistently greater than 98%. In some experiments, purified CD4+/CD45RA+ cells were frozen in aliquots of 107/mL in RPMI-1640 medium containing 20% fetal calf serum (FCS) and 10% dimethyl sulfoxide for use at a later date. Viability after thawing was consistently greater than 90%.In vitro activation of DC1 and DC2 Purified DC1 and DC2 were cultured for 2 to 6 days in flat-bottomed 96-well plates at 10 to 50 × 103 cells/ 200 µL in complete RPMI-HEPES containing 10% heat-inactivated FCS (Gibco BRL, Grand Island, NY). The following cytokines were added: 10 ng/mL (150 IU/mL) human recombinant GM-CSF (Genzyme, Cambridge, MA), 50 ng/mL human recombinant IL-3 (R&D Systems, Minneapolis, MN), and 10 ng/mL (1100 IU/mL) human recombinant TNF- (R&D Systems).
T-cell proliferation assays Fresh or in vitro-activated DC1 and DC2 were cocultured with autologous or allogeneic naive CD4+CD45RA+ cells to test for stimulatory activity. Stimulator cells were suspended in complete medium containing 15% FCS and irradiated at 1500 cGy, and serial dilutions were prepared beginning at 5 to 10 × 103 cells/well. Responding T cells were plated at 5 × 104 cells/well. All cocultures were performed in round-bottomed 96-well plates. Cultures were maintained in a humidified atmosphere at 37°C and 5% CO2. Cultures were pulsed with 1 µCi/well 3H-thymidine for 8 to 18 hours before harvest on day 6 to measure proliferation.Cytokine production assay Naive CD4+CD45RA+ T cells were cocultured with allogeneic DC1 and DC2, harvested after 6 days, and replated at 5 × 104 cells/well in round-bottomed 96-well plates in the presence of PMA (25 ng/mL) and ionomycin (1 µg/mL). After 48 hours supernatants were harvested and frozen until analysis. Cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA). ELISA kits for human IFN- , IL-4, and IL-10 were purchased from Endogen (Boston,
MA). The lower limits of detection were 2.6 pg/mL for IFN- , 2.8 pg/mL for IL-10, and 3 pg/mL for IL-4. Specific activity of
rH IFN- and IL-4 used in the assay were,
respectively, 6.8 × 103 and
2.9 × 104 IU/µg. Specific activity was not
available for IL-10.
Statistical analysis Proliferation and cytokine data are summarized with means ± 1 SD. Statistical comparisons were performed using t tests for independent samples.
Phenotype of dendritic cells in the peripheral blood of normal and G-CSF-treated donors DC were identified as HLA-DR+ cells and negative for granulocytes, monocytes, natural kill cells, T cells, B cells, and CD34 cell lineage markers (Figure 1A), and they constituted on average 0.5% PBMC from normal donors. They showed light scatter properties intermediate between lymphocytes and monocytes (Figures 1B, 1C). They were larger and more granular than resting lymphocytes but smaller and less granular than monocytes. DC were analyzed for the expression of the adhesion molecule CD11c, typical of DC1 lineage, and of the IL-3 receptor (IL-3R) chain typically bright in the DC2
lineage (Figure 1D). The intensity of CD4 expression was higher on DC2
(Figure 1E) than on DC1. DC from G-CSF-treated donors showed the same
pattern of expression of CD11c, IL-3R , and CD4 as in normal donors
(Figures 1D, 1E) and the same light scatter properties (Figure 1C).
G-CSF treatment mobilizes DC2 but not DC1 G-CSF treatment induces mobilization of leukocytes into the bloodstream. In our series, the median WBC count was 5500 × 106/L in normal donors and 31,200 × 106/L in G-CSF-treated donors. The increase in the number of leukocytes in the blood of G-CSF-treated patients was mainly caused by the mobilization of granulocytes and monocytes (data not shown). The median DC1 count was not different in normal or G-CSF-treated donors (Figure 2 ). In contrast, the median DC2 count was 4.9 × 106/L (range, 1.9-10.8 × 106/L) in the blood of normal donors and 5-fold higher at 24.8 × 106/L (range 7.9-45.5 × 106/L) in the blood of G-CSF treated donors (P = .0009) (Figure 2). Therefore, the ratio between DC2 and DC1 was higher in G-CSF-treated donors as a consequence of the selective increase of DC2.
Proliferative response of naive allogeneic T cells to fresh DC1 but not DC2 DC1 and DC2 were purified as described in "Materials and methods" (Figure 3) and then tested for their ability to induce the proliferation of allogeneic naive T cells because this is a specific function of DC. DC1 obtained from the same donor before and after G-CSF treatment were both powerful stimulators of naive allogeneic but not autologous T cells (Figures 4A to 4C). In contrast, DC2 induced weak, if any, proliferation of naive allogeneic T cells. Thus, in normal and in G-CSF-treated donors, fresh DC1 but not DC2 can induce allogeneic naive T cells to proliferate in vitro.
Proliferative response of naive allogeneic T cells to activated DC2 The difference in stimulatory ability between fresh DC1 and DC2 could result from their level of expression of costimulatory molecules or state of cell activation. Reports from several laboratories have indicated that costimulatory molecules CD40, CD80, and CD86 are expressed at low levels on resting DC1 and at even lower levels on resting DC2 isolated from human blood.29-31 We tested whether DC2 activation with cytokines would induce allo-stimulatory activity. DC2 from G-CSF-treated donors did not express CD40, CD80, or CD86 (Figure 5, upper panel). Purified DC1 and DC2 were activated in vitro for 48 hours with GM-CSF, IL-3, and TNF- . GM-CSF and IL-3 were chosen because they are
essential for the survival of DC115,26,30 and
DC2,27,28,30 respectively, and TNF- was used to activate the expression of CD86 and antigen-presenting
function.18,21 After activation, DC2 from G-CSF-treated
donors up-regulated the expression of CD40, CD80, and CD86 (Figure 5,
lower panel). When used to stimulate naive allogeneic
CD4+CD45RA+ T cells, activated DC1 and DC2 were
both able to stimulate T-cell proliferation, whether they were obtained
from untreated or G-CSF-treated donors (Figures 4B to 4D).
Th2 polarization of naive allogeneic T cells stimulated by activated DC2 To assess Th1 versus Th2 polarization, CD4+CD45RA+ naive T cells were cultured with activated DC1 or DC2 from G-CSF-treated allogeneic donors and restimulated with PMA plus ionomycin to release cytokines in the supernatant. T cells primed by DC1 produced predominantly IFN-
whereas T cells primed by DC2 produced predominantly IL-10 and IL-4
(Figure 6). T cells primed by DC from
normal donors showed the same pattern of cytokine production, depending
on the DC subset (not shown). Thus, in G-CSF-treated and normal donors, activated DC1 induced naive allogeneic T cells to differentiate into
IFN- -producing effector Th1 cells, whereas activated DC2 induced
naive allogeneic T cells to differentiate into IL-4 and IL-10-producing
effector Th2 cells.
Recipients of unmodified blood stem cell products from G-CSF-treated donors receive more DC2 than recipients of unmodified marrow products DC were identified in normal marrow by their lineage , HLA-DR+, CD4+, and
CD11c+ (DC1) or IL-3R + (DC2) phenotype (not
shown). We determined the count of DC1 and DC2 in a series of samples
from either marrow or blood stem cell products from G-CSF-treated
donors, collected for the purpose of allogeneic transplantation. The
dose of total nucleated cells received by recipients of blood stem
cells (median, 743.8 × 106/kg body weight)
(n = 7) was higher than for recipients of marrow transplants (median,
256.1 × 106/kg body weight) (n = 15). The DC1
dose did not differ between recipients of marrow and blood stem cells
(Figure 7). In contrast, the dose of DC2
received by recipients of blood stem cells from G-CSF-treated donors
(median, 2.4 × 106/kg body weight, n = 7) was
higher than the dose received by recipients of marrow transplants
(median, 0.5 × 106/kg body weight, n = 15)
(P = .006; Figure 7). Thus, in this study, recipients of
G-CSF-mobilized blood stem cells received more Th2-inducing antigen-presenting cells than recipients of marrow transplants.
Antigen-specific T-cell responses are characterized by
distinct profiles of secreted cytokines. Here we have confirmed recent findings by Rissoan et al15 demonstrating that polarization of the T-cell response into Th1 or Th2 depends on the type of antigen-presenting cell: in humans, CD11c+ DC1 induce Th1
responses, whereas IL-3R
We thank Dr Michael Loken for his expert assistance in the design of the 4-color flow microfluorometric assays and Jennifer Brackensick for typing the manuscript.
Submitted July 14, 1999; accepted December 13, 1999.
Supported by National Institutes of Health grants AI33484, AI37678, and CA18029.
Reprints not available from the author.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
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E. S. Morris, K. P. A. MacDonald, and G. R. Hill Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood, May 1, 2006; 107(9): 3430 - 3435. [Abstract] [Full Text] [PDF] |
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D.-P. Lu, L. Dong, T. Wu, X.-J. Huang, M.-J. Zhang, W. Han, H. Chen, D.-H. Liu, Z.-Y. Gao, Y.-H. Chen, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation Blood, April 15, 2006; 107(8): 3065 - 3073. [Abstract] [Full Text] [PDF] |
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Z. F. M. Vasconcelos, B. M. dos Santos, J. Farache, T. S. S. Palmeira, R. B. Areal, J. M. T. Cunha, M. A. Barcinski, and A. Bonomo G-CSF-treated granulocytes inhibit acute graft-versus-host disease Blood, March 1, 2006; 107(5): 2192 - 2199. [Abstract] [Full Text] [PDF] |
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S. Rutella, F. Zavala, S. Danese, H. Kared, and G. Leone Granulocyte Colony-Stimulating Factor: A Novel Mediator of T Cell Tolerance J. Immunol., December 1, 2005; 175(11): 7085 - 7091. [Abstract] [Full Text] [PDF] |
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M. Rossi and J. W. Young Human Dendritic Cells: Potent Antigen-Presenting Cells at the Crossroads of Innate and Adaptive Immunity J. Immunol., August 1, 2005; 175(3): 1373 - 1381. [Abstract] [Full Text] [PDF] |
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B. Drenou, L. Amiot, N. Setterblad, S. Taque, V. Guilloux, D. Charron, R. Fauchet, and N. Mooney MHC class II signaling function is regulated during maturation of plasmacytoid dendritic cells J. Leukoc. Biol., April 1, 2005; 77(4): 560 - 567. [Abstract] [Full Text] [PDF] |
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H. Gur, R. Krauthgamer, E. Bachar-Lustig, H. Katchman, R. Arbel-Goren, A. Berrebi, T. Klein, A. Nagler, A. Tabilio, M. F. Martelli, et al. Immune regulatory activity of CD34+ progenitor cells: evidence for a deletion-based mechanism mediated by TNF-{alpha} Blood, March 15, 2005; 105(6): 2585 - 2593. [Abstract] [Full Text] [PDF] |
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K. P. A. MacDonald, V. Rowe, A. D. Clouston, J. K. Welply, R. D. Kuns, J. L. M. Ferrara, R. Thomas, and G. R. Hill Cytokine Expanded Myeloid Precursors Function as Regulatory Antigen-Presenting Cells and Promote Tolerance through IL-10-Producing Regulatory T Cells J. Immunol., February 15, 2005; 174(4): 1841 - 1850. [Abstract] [Full Text] [PDF] |
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I. J. Fugier-Vivier, F. Rezzoug, Y. Huang, A. J. Graul-Layman, C. L. Schanie, H. Xu, P. M. Chilton, and S. T. Ildstad Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment J. Exp. Med., February 7, 2005; 201(3): 373 - 383. [Abstract] [Full Text] [PDF] |
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K. McKenna, A.-S. Beignon, and N. Bhardwaj Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity J. Virol., January 1, 2005; 79(1): 17 - 27. [Full Text] [PDF] |
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H. Kared, A. Masson, H. Adle-Biassette, J.-F. Bach, L. Chatenoud, and F. Zavala Treatment With Granulocyte Colony-Stimulating Factor Prevents Diabetes in NOD Mice by Recruiting Plasmacytoid Dendritic Cells and Functional CD4+CD25+ Regulatory T-Cells Diabetes, January 1, 2005; 54(1): 78 - 84. [Abstract] [Full Text] [PDF] |
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M. Eapen, M. M. Horowitz, J. P. Klein, R. E. Champlin, F. R. Loberiza Jr, O. Ringden, and J. E. Wagner Higher Mortality After Allogeneic Peripheral-Blood Transplantation Compared With Bone Marrow in Children and Adolescents: The Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry J. Clin. Oncol., December 15, 2004; 22(24): 4872 - 4880. [Abstract] [Full Text] [PDF] |
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G. Le Friec, F. Gros, Y. Sebti, V. Guilloux, C. Pangault, R. Fauchet, and L. Amiot Capacity of myeloid and plasmacytoid dendritic cells especially at mature stage to express and secrete HLA-G molecules J. Leukoc. Biol., December 1, 2004; 76(6): 1125 - 1133. [Abstract] [Full Text] [PDF] |
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T. Crough, M. Nieda, and A. J. Nicol Granulocyte Colony-Stimulating Factor Modulates {alpha}-Galactosylceramide-Responsive Human V{alpha}24+V{beta}11+ NKT Cells J. Immunol., October 15, 2004; 173(8): 4960 - 4966. [Abstract] [Full Text] [PDF] |
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E. A. Moseman, X. Liang, A. J. Dawson, A. Panoskaltsis-Mortari, A. M. Krieg, Y.-J. Liu, B. R. Blazar, and W. Chen Human Plasmacytoid Dendritic Cells Activated by CpG Oligodeoxynucleotides Induce the Generation of CD4+CD25+ Regulatory T Cells J. Immunol., October 1, 2004; 173(7): 4433 - 4442. [Abstract] [Full Text] [PDF] |
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K. E. Lawlor, I. K. Campbell, D. Metcalf, K. O'Donnell, A. van Nieuwenhuijze, A. W. Roberts, and I. P. Wicks Critical role for granulocyte colony-stimulating factor in inflammatory arthritis PNAS, August 3, 2004; 101(31): 11398 - 11403. [Abstract] [Full Text] [PDF] |
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F. F. Fagnoni, B. Oliviero, G. Giorgiani, P. De Stefano, A. Deho, C. Zibera, N. Gibelli, R. Maccario, G. Da Prada, M. Zecca, et al. Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation Blood, July 1, 2004; 104(1): 281 - 289. [Abstract] [Full Text] [PDF] |
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N. Teleshova, J. Jones, J. Kenney, J. Purcell, R. Bohm, A. Gettie, and M. Pope Short-term Flt3L treatment effectively mobilizes functional macaque dendritic cells J. Leukoc. Biol., June 1, 2004; 75(6): 1102 - 1110. [Abstract] [Full Text] [PDF] |
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V. Reddy, J. A. Iturraspe, A. C. Tzolas, H.-U. Meier-Kriesche, J. Schold, and J. R. Wingard Low dendritic cell count after allogeneic hematopoietic stem cell transplantation predicts relapse, death, and acute graft-versus-host disease Blood, June 1, 2004; 103(11): 4330 - 4335. [Abstract] [Full Text] [PDF] |
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E. Chklovskaia, P. Nowbakht, C. Nissen, A. Gratwohl, M. Bargetzi, and A. Wodnar-Filipowicz Reconstitution of dendritic and natural killer-cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand Blood, May 15, 2004; 103(10): 3860 - 3868. [Abstract] [Full Text] [PDF] |
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P. Bjorck Dendritic Cells Exposed to Herpes Simplex Virus In Vivo Do Not Produce IFN-{alpha} after Rechallenge with Virus In Vitro and Exhibit Decreased T Cell Alloreactivity J. Immunol., May 1, 2004; 172(9): 5396 - 5404. [Abstract] [Full Text] [PDF] |
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E. S. Morris, K. P. A. MacDonald, V. Rowe, D. H. Johnson, T. Banovic, A. D. Clouston, and G. R. Hill Donor treatment with pegylated G-CSF augments the generation of IL-10-producing regulatory T cells and promotes transplantation tolerance Blood, May 1, 2004; 103(9): 3573 - 3581. [Abstract] [Full Text] [PDF] |
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W. Chen, S. Antonenko, J. M. Sederstrom, X. Liang, A. S. H. Chan, H. Kanzler, B. Blom, B. R. Blazar, and Y.-J. Liu Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors Blood, April 1, 2004; 103(7): 2547 - 2553. [Abstract] [Full Text] [PDF] |
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O. Ringden, M. Labopin, N.-C. Gorin, K. Le Blanc, V. Rocha, E. Gluckman, J. Reiffers, W. Arcese, J. M. Vossen, J.-P. Jouet, et al. Treatment With Granulocyte Colony-Stimulating Factor After Allogeneic Bone Marrow Transplantation for Acute Leukemia Increases the Risk of Graft-Versus-Host Disease and Death: A Study From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation J. Clin. Oncol., February 1, 2004; 22(3): 416 - 423. [Abstract] [Full Text] [PDF] |
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A. Kaser, S. Kaser, N. C. Kaneider, B. Enrich, C. J. Wiedermann, and H. Tilg Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression Blood, January 15, 2004; 103(2): 648 - 655. [Abstract] [Full Text] [PDF] |
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M. Salio, N. Dulphy, J. Renneson, M. Herbert, A. McMichael, A. Marchant, and V. Cerundolo Efficient priming of antigen-specific cytotoxic T lymphocytes by human cord blood dendritic cells Int. Immunol., October 1, 2003; 15(10): 1265 - 1273. [Abstract] [Full Text] [PDF] |
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S. Miyazaki, H. Tsuda, M. Sakai, S. Hori, Y. Sasaki, T. Futatani, T. Miyawaki, and S. Saito Predominance of Th2-promoting dendritic cells in early human pregnancy decidua J. Leukoc. Biol., October 1, 2003; 74(4): 514 - 522. [Abstract] [Full Text] [PDF] |
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R. A. Nash, J. D. Bowen, P. A. McSweeney, S. Z. Pavletic, K. R. Maravilla, M.-s. Park, J. Storek, K. M. Sullivan, J. Al-Omaishi, J. R. Corboy, et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis Blood, October 1, 2003; 102(7): 2364 - 2372. [Abstract] [Full Text] [PDF] |
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P. T. H. Coates, S. M. Barratt-Boyes, L. Zhang, V. S. Donnenberg, P. J. O'Connell, A. J. Logar, F. J. Duncan, M. Murphey-Corb, A. D. Donnenberg, A. E. Morelli, et al. Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand Blood, October 1, 2003; 102(7): 2513 - 2521. [Abstract] [Full Text] [PDF] |
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M. Jefford, M. Schnurr, T. Toy, K.-A. Masterman, A. Shin, T. Beecroft, T. Y. Tai, K. Shortman, M. Shackleton, I. D. Davis, et al. Functional comparison of DCs generated in vivo with Flt3 ligand or in vitro from blood monocytes: differential regulation of function by specific classes of physiologic stimuli Blood, September 1, 2003; 102(5): 1753 - 1763. [Abstract] [Full Text] [PDF] |
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J. A. Perez-Simon, M. Diez-Campelo, R. Martino, A. Sureda, D. Caballero, C. Canizo, S. Brunet, A. Altes, L. Vazquez, J. Sierra, et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation Blood, August 1, 2003; 102(3): 1108 - 1113. [Abstract] [Full Text] [PDF] |
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A. Franzke, W. Piao, J. Lauber, P. Gatzlaff, C. Konecke, W. Hansen, A. Schmitt-Thomsen, B. Hertenstein, J. Buer, and A. Ganser G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases Blood, July 15, 2003; 102(2): 734 - 739. [Abstract] [Full Text] [PDF] |
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S. Senju, S. Hirata, H. Matsuyoshi, M. Masuda, Y. Uemura, K. Araki, K.-i. Yamamura, and Y. Nishimura Generation and genetic modification of dendritic cells derived from mouse embryonic stem cells Blood, May 1, 2003; 101(9): 3501 - 3508. [Abstract] [Full Text] [PDF] |
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S. Vuckovic, M. Kim, D. Khalil, C. J. Turtle, G. V. Crosbie, N. Williams, L. Brown, K. Williams, C. Kelly, P. Stravos, et al. Granulocyte-colony stimulating factor increases CD123hi blood dendritic cells with altered CD62L and CCR7 expression Blood, March 15, 2003; 101(6): 2314 - 2317. [Abstract] [Full Text] [PDF] |
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K. P. A. MacDonald, V. Rowe, C. Filippich, R. Thomas, A. D. Clouston, J. K. Welply, D. N. J. Hart, J. L. M. Ferrara, and G. R. Hill Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation Blood, March 1, 2003; 101(5): 2033 - 2042. [Abstract] [Full Text] [PDF] |
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G. Ratzinger, J. L. Reagan, G. Heller, K. J. Busam, and J. W. Young Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation Blood, February 15, 2003; 101(4): 1422 - 1429. [Abstract] [Full Text] [PDF] |
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I. D. Davis, M. Jefford, P. Parente, and J. Cebon Rational approaches to human cancer immunotherapy J. Leukoc. Biol., January 1, 2003; 73(1): 3 - 29. [Abstract] [Full Text] [PDF] |
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M. H. Cottler-Fox, T. Lapidot, I. Petit, O. Kollet, J. F. DiPersio, D. Link, and S. Devine Stem Cell Mobilization Hematology, January 1, 2003; 2003(1): 419 - 437. [Abstract] [Full Text] [PDF] |
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M. J. Robertson, D. Pelloso, R. Abonour, R. A. Hromas, R. P. Nelson Jr., L. Wood, and K. Cornetta Interleukin 12 Immunotherapy after Autologous Stem Cell Transplantation for Hematological Malignancies Clin. Cancer Res., November 1, 2002; 8(11): 3383 - 3393. [Abstract] [Full Text] [PDF] |
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M. Mohty, M. Kuentz, M. Michallet, J.-H. Bourhis, N. Milpied, L. Sutton, J.-P. Jouet, M. Attal, P. Bordigoni, J.-Y. Cahn, et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study Blood, October 16, 2002; 100(9): 3128 - 3134. [Abstract] [Full Text] [PDF] |
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H. Matsuda, T. Suda, H. Hashizume, K. Yokomura, K. Asada, K. Suzuki, K. Chida, and H. Nakamura Alteration of Balance between Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in Peripheral Blood of Patients with Asthma Am. J. Respir. Crit. Care Med., October 15, 2002; 166(8): 1050 - 1054. [Abstract] [Full Text] [PDF] |
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H. J. Bontkes, T. D. de Gruijl, G. J. Schuurhuis, R. J. Scheper, C. J. L. M. Meijer, and E. Hooijberg Expansion of dendritic cell precursors from human CD34+ progenitor cells isolated from healthy donor blood; growth factor combination determines proliferation rate and functional outcome J. Leukoc. Biol., August 1, 2002; 72(2): 321 - 329. [Abstract] [Full Text] [PDF] |
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V. Lapierre, A. Auperin, H. Tayebi, J. Chabod, P. Saas, M. Michalet, S. Francois, F. Garban, C. Giraud, D. Tramalloni, et al. Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation Blood, July 30, 2002; 100(4): 1484 - 1489. [Abstract] [Full Text] [PDF] |
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G. Gorgun, K. B. Miller, and F. M. Foss Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease Blood, July 18, 2002; 100(3): 941 - 947. [Abstract] [Full Text] [PDF] |
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R. Handgretinger, P. Lang, T. Klingebiel, D. Niethammer ;, R. Storb, P. J. Martin, J. M. Zaucha, W. I. Bensinger, M. E. D. Flowers, G. Georges, et al. CD34 stem cell dose and development of extensive chronic graft-versus-host disease Blood, May 15, 2002; 99(10): 3875 - 3877. [Full Text] [PDF] |
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M. Gilliet and Y.-J. Liu Generation of Human CD8 T Regulatory Cells by CD40 Ligand-activated Plasmacytoid Dendritic Cells J. Exp. Med., March 11, 2002; 195(6): 695 - 704. [Abstract] [Full Text] [PDF] |
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F. Zavala, S. Abad, S. Ezine, V. Taupin, A. Masson, and J.-F. Bach G-CSF Therapy of Ongoing Experimental Allergic Encephalomyelitis Via Chemokine- and Cytokine-Based Immune Deviation J. Immunol., February 15, 2002; 168(4): 2011 - 2019. [Abstract] [Full Text] [PDF] |
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S. Auffermann-Gretzinger, I. S. Lossos, T. A. Vayntrub, W. Leong, F. C. Grumet, K. G. Blume, K. E. Stockerl-Goldstein, R. Levy, and J. A. Shizuru Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients Blood, February 15, 2002; 99(4): 1442 - 1448. [Abstract] [Full Text] [PDF] |
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J. E. Levine, T. Braun, S. L. Penza, P. Beatty, K. Cornetta, R. Martino, W. R. Drobyski, A. J. Barrett, D. L. Porter, S. Giralt, et al. Prospective Trial of Chemotherapy and Donor Leukocyte Infusions for Relapse of Advanced Myeloid Malignancies After Allogeneic Stem-Cell Transplantation J. Clin. Oncol., January 15, 2002; 20(2): 405 - 412. [Abstract] [Full Text] [PDF] |
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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] |
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M. Mohty, D. Jarrossay, M. Lafage-Pochitaloff, C. Zandotti, F. Briere, X.-N. de Lamballeri, D. Isnardon, D. Sainty, D. Olive, and B. Gaugler Circulating blood dendritic cells from myeloid leukemia patients display quantitative and cytogenetic abnormalities as well as functional impairment Blood, December 15, 2001; 98(13): 3750 - 3756. [Abstract] [Full Text] [PDF] |
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M. Korbling and P. Anderlini Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood, November 15, 2001; 98(10): 2900 - 2908. [Abstract] [Full Text] [PDF] |
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A. Urbano-Ispizua, E. Carreras, P. Marin, M. Rovira, C. Martinez, F. Fernandez-Aviles, B. Xicoy, J.-C. Hernandez-Boluda, and E. Montserrat Allogeneic transplantation of CD34+ selected cells from peripheral blood from human leukocyte antigen-identical siblings: detrimental effect of a high number of donor CD34+ cells? Blood, October 15, 2001; 98(8): 2352 - 2357. [Abstract] [Full Text] [PDF] |
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M. B. Faries, I. Bedrosian, S. Xu, G. Koski, J. G. Roros, M. A. Moise, H. Q. Nguyen, F. H. C. Engels, P. A. Cohen, and B. J. Czerniecki Calcium signaling inhibits interleukin-12 production and activates CD83+ dendritic cells that induce Th2 cell development Blood, October 15, 2001; 98(8): 2489 - 2497. [Abstract] [Full Text] [PDF] |
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D. Przepiorka, P. Anderlini, R. Saliba, K. Cleary, R. Mehra, I. Khouri, Y. O. Huh, S. Giralt, I. Braunschweig, K. van Besien, et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation Blood, September 15, 2001; 98(6): 1695 - 1700. [Abstract] [Full Text] [PDF] |
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C. Cutler, S. Giri, S. Jeyapalan, D. Paniagua, A. Viswanathan, and J. H. Antin Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis J. Clin. Oncol., August 15, 2001; 19(16): 3685 - 3691. [Abstract] [Full Text] [PDF] |
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P. Schwarzenberger, W. Huang, P. Oliver, P. Byrne, V. La Russa, Z. Zhang, and J. K. Kolls IL-17 Mobilizes Peripheral Blood Stem Cells with Short- and Long-Term Repopulating Ability in Mice J. Immunol., August 15, 2001; 167(4): 2081 - 2086. [Abstract] [Full Text] [PDF] |
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V. Soumelis, I. Scott, F. Gheyas, D. Bouhour, G. Cozon, L. Cotte, L. Huang, J. A. Levy, and Y.-J. Liu Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients Blood, August 15, 2001; 98(4): 906 - 912. [Abstract] [Full Text] [PDF] |
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C. W. Cutler, R. Jotwani, and B. Pulendran Dendritic Cells: Immune Saviors or Achilles' Heel? Infect. Immun., August 1, 2001; 69(8): 4703 - 4708. [Full Text] [PDF] |
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G.B. Toews Cytokines and the lung Eur. Respir. J., July 2, 2001; 18(34_suppl): 3S - 17s. [Abstract] [Full Text] [PDF] |
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C. S. K. Ho, J. A. Lopez, S. Vuckovic, C. M. Pyke, R. L. Hockey, and D. N. J. Hart Surgical and physical stress increases circulating blood dendritic cell counts independently of monocyte counts Blood, July 1, 2001; 98(1): 140 - 145. [Abstract] [Full Text] [PDF] |
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N. Kadowaki, S. Antonenko, S. Ho, M.-C. Rissoan, V. Soumelis, S. A. Porcelli, L. L. Lanier, and Y.-J. Liu Distinct Cytokine Profiles of Neonatal Natural Killer T Cells after Expansion with Subsets of Dendritic Cells J. Exp. Med., May 21, 2001; 193(10): 1221 - 1226. [Abstract] [Full Text] [PDF] |
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E. K. Waller, H. Rosenthal, T. W. Jones, J. Peel, S. Lonial, A. Langston, I. Redei, I. Jurickova, and M. W. Boyer Larger numbers of CD4bright dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation Blood, May 15, 2001; 97(10): 2948 - 2956. [Abstract] [Full Text] [PDF] |
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I. Volpi, K. Perruccio, A. Tosti, M. Capanni, L. Ruggeri, S. Posati, F. Aversa, A. Tabilio, L. Romani, M. F. Martelli, et al. Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants Blood, April 15, 2001; 97(8): 2514 - 2521. [Abstract] [Full Text] [PDF] |
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M. Rosenzweig, M. Connole, R. Glickman, S.-P. S. Yue, B. Noren, M. DeMaria, and R. P. Johnson Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34+ hematopoietic cells Blood, April 1, 2001; 97(7): 1951 - 1959. [Abstract] [Full Text] [PDF] |
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W. I. Bensinger, P. J. Martin, B. Storer, R. Clift, S. J. Forman, R. Negrin, A. Kashyap, M. E.D. Flowers, K. Lilleby, T. R. Chauncey, et al. Transplantation of Bone Marrow as Compared with Peripheral-Blood Cells from HLA-Identical Relatives in Patients with Hematologic Cancers N. Engl. J. Med., January 18, 2001; 344(3): 175 - 181. [Abstract] [Full Text] [PDF] |
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M. Sivakumaran, Z. F. M. Vasconcelos, H. R. Diamond, D. G. Tabak, M. A. Barcinski, A. Bonomo, E. Sloand, S. Kim, J. Maciejewski, and N. Young Modulation of Th1/Th2 subsets by granulocyte-colony stimulating factor Blood, January 1, 2001; 97(1): 333 - 335. [Full Text] [PDF] |
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J. Banchereau, B. Pulendran, R. Steinman, and K. Palucka Will the Making of Plasmacytoid Dendritic Cells in Vitro Help Unravel Their Mysteries? J. Exp. Med., December 18, 2000; 192(12): f39 - f44. [Full Text] [PDF] |
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B. Blom, S. Ho, S. Antonenko, and Y.-J. Liu Generation of Interferon {alpha}-Producing Predendritic Cell (Pre-Dc)2 from Human Cd34+ Hematopoietic Stem Cells J. Exp. Med., December 18, 2000; 192(12): 1785 - 1796. [Abstract] [Full Text] [PDF] |
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V. Reddy Granulocyte colony-stimulating factor mobilization alters dendritic cell cytokine production and initiates T helper 2 polarization prior to host alloantigen presentation Blood, October 1, 2000; 96(7): 2635 - 2635. [Full Text] [PDF] |
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Y.-J. Liu and B. Blom Introduction: TH2-inducing DC2 for immunotherapy Blood, April 15, 2000; 95(8): 2482 - 2483. [Full Text] [PDF] |
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M. Brenner, C. Rossig, U. Sili, J. W. Young, and E. Goulmy Transfusion Medicine: New Clinical Applications of Cellular Immunotherapy Hematology, January 1, 2000; 2000(1): 356 - 375. [Abstract] [Full Text] [PDF] |
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M. Gilliet, A. Boonstra, C. Paturel, S. Antonenko, X.-L. Xu, G. Trinchieri, A. O'Garra, and Y.-J. Liu The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor J. Exp. Med., April 1, 2002; 195(7): 953 - 958. [Abstract] [Full Text] [PDF] |
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