GM-CSF in the generation of dendritic cells from human blood monocyte precursors: Recent advances

Conti, Lucia; Gessani, Sandra

doi:10.1016/j.imbio.2008.07.017

Cited by 85 publications

(82 citation statements)

References 80 publications

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“…6), which also has been reported earlier [31]. Several protocols describe the generation of DCs in vitro with respect to cell sources, cytokine concentrations, or culture period [32,33]. Although differentiated MoDCs and peripheral mDCs have shown expression of the same investigated surface markers, expression of surface markers by the generated DCs does not always reflect the functionality of the cells and other groups have reported that MoDCs and mDCs may differ in several ways, for example by their cytokine production in response to pathogen signals and ability to stimulate T lymphocytes [13,34].…”

Section: Discussionmentioning

confidence: 60%

Myeloid blood dendritic cells and monocyte-derived dendritic cells differ in their endocytosing capability

et al. 2012

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a b s t r a c tHuman dendritic cells (DCs) constitute a heterogeneous population of antigen-presenting cells characterized by a unique capacity to stimulate naïve T cells. The functions of DCs depend on the particular subset and in this study we compare two types of myeloid DCs: freshly isolated blood mDCs and in vitro generated monocyte-derived DCs (MoDCs), in their ability to accomplish endocytosis.In our hands, these two DC subtypes showed similarities in the expression of surface markers, but displayed clear differences in endocytic capacity. Freshly isolated blood mDCs showed a high propensity to capture and endocytose particles compared to in vitro generated MoDCs. The blood mDCs also showed a clear receptor-enhanced endocytosis when zeolite particles were co-adsorbed with IgG. On the other hand, the MoDCs differed remarkably compared to blood mDCs in the capture of ovalbumin and immune complexes. Interestingly, the MoDCs showed low endocytosis of IgG-coated particles but an efficient capture of immune complexes. The MoDCs also showed a high capacity to capture ovalbumin although with a relatively low degree of internalization. These data indicate distinct differences in the early process of endocytosis featured by mDCs and MoDCs, which is important to consider when choosing DC populations for future functional or clinical applications. Ó

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Section: Discussionmentioning

confidence: 60%

Myeloid blood dendritic cells and monocyte-derived dendritic cells differ in their endocytosing capability

et al. 2012

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“…This induced the differentiation of circulating inflammatory monocytes into inflammatory DCs and resulted in effective immune responses. [41][42][43][44] Insufficient stimulation with GM-CSF, on the other hand, can result in the production of immature DCs, or so-called tolerogenic DCs (tolDCs), that lead to tolerogenic responses in vivo. 45,46 Thus, correct use of GM-CSF is the key to inducing effective immunity.…”

Section: Discussionmentioning

confidence: 99%

“…A similar result was reported with a long-lasting polyethylene glycol-modified GM-CSF causing the expansion of CD11b 1 CD11c 1 dendritic cells in vivo. 35,42,48 To delineate the possible cumulative effects of sequential stimulation, a comparison was made with 30 mg of GM-CSF given to mice as a single injection. Although the effects were much greater than those from one or two low (10 mg) daily doses, its inferiority in terms of breaking immune tolerance was evidenced when the levels of induced anti-HBsAg antibodies, CTLs and HBsAg-positive hepatocyte clearance were compared.…”

Section: Discussionmentioning

confidence: 99%

Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice

Wang

Dong²,

Xiao

et al. 2015

Cell Mol Immunol

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-c production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8 1 T cells from immunized animals, antigen-specific CD8 1 T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients. Cellular & Molecular Immunology

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“…In recent years, major advances have been made in the identification of DC precursors and methods to expand and manipulate these cells ex vivo. Monocyte-derived DCs, which are morphologically and phenotypically similar to blood DCs, are the DC preparations most widely used for experimental and clinical purposes (11,(35)(36)(37)(38). In addition, significant efforts have been made to use cultured DCs pulsed with tumor antigens to induce antitumor immunity (31,39).…”

Section: Discussionmentioning

confidence: 99%

A Suppressor of Cytokine Signaling 1 Antagonist Enhances Antigen-Presenting Capacity and Tumor Cell Antigen-Specific Cytotoxic T Lymphocyte Responses by Human Monocyte-Derived Dendritic Cells

Wang

Yuan

et al. 2013

Clin Vaccine Immunol

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The suppressor of cytokine signaling 1 (SOCS1) has emerged as a critical inhibitory molecule for controlling the cytokine response and antigen presentation by dendritic cells (DCs), thereby regulating the magnitude of both innate and adaptive immunity. The aim of this study was to investigate whether the SOCS1 antagonist pJAK2(1001-1013) peptide can weaken or block the inhibition function of SOCS1 in DCs by evaluating the phenotype and cytokine production, antigen-presenting, and specific Tcell-activating capacities of DCs electroporated with human gastric cancer cell total RNA. Furthermore, STAT1 activation of the JAK/STAT signal pathway mediated by SOCS1 was analyzed by Western blotting. The results demonstrate that the SOCS1 antagonist pJAK2(1001-1013) peptide upregulated the expression of the maturation marker (CD83) and costimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature DCs (mDCs), potentiated the capacity of mDCs to induce Tcell proliferation, stimulated the secretion of proinflammatory cytokines, and enhanced the cytotoxicity of tumor cell antigenspecific CTLs activated by human gastric cancer cell total RNA-electroporated mDCs. Data from Western blot analysis indicate that STAT1 was further activated in pJAK2(1001-1013) peptide-loaded mDCs. These results imply that the SOCS1 antagonist pJAK2(1001-1013) peptide is an effective reagent for the enhancement of antigen-specific antitumor immunity by DCs.

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GM-CSF in the generation of dendritic cells from human blood monocyte precursors: Recent advances

Cited by 85 publications

References 80 publications

Myeloid blood dendritic cells and monocyte-derived dendritic cells differ in their endocytosing capability

Myeloid blood dendritic cells and monocyte-derived dendritic cells differ in their endocytosing capability

Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice

A Suppressor of Cytokine Signaling 1 Antagonist Enhances Antigen-Presenting Capacity and Tumor Cell Antigen-Specific Cytotoxic T Lymphocyte Responses by Human Monocyte-Derived Dendritic Cells

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