Monocyte-Derived Dendritic Cells Generated After a Short-Term Culture with IFN-α and Granulocyte-Macrophage Colony-Stimulating Factor Stimulate a Potent Epstein-Barr Virus-Specific CD8+ T Cell Response

Santodonato, Laura; D’Agostino, Giuseppina; Nisini, Roberto; Mariotti, Sabrina; Monque, Domenica M.; Spada, Massimo; Lattanzi, Laura; Perrone, Maria Paola; Andreotti, Mauro; Belardelli, Filippo; Ferrantini, Maria

doi:10.4049/jimmunol.170.10.5195

Cited by 76 publications

(52 citation statements)

References 41 publications

(39 reference statements)

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“…1, top panels, and Table I). Consistent with previous reports (11)(12)(13)(14)(15), IFN-␣ DCs expressed higher levels of CD40, CD80, CD86, and HLA-DR relative to control DCs before LPS stimulation (Fig. 1).…”

Section: Increased Migration Of Ifn-␣ Dcs Mediated By Ccr5 and Ccr1supporting

confidence: 81%

“…Similar to the approaches taken in previous reports (11)(12)(13)(14)(15), IFN-␣ DCs were generated from human CD14 ϩ monocytes by culturing cells for 5 days with IFN-␣ and GM-CSF. Control monocyte-derived DCs were obtained using the well-established approach of culture with IL-4 and GM-CSF (16).…”

Section: Increased Migration Of Ifn-␣ Dcs Mediated By Ccr5 and Ccr1mentioning

confidence: 99%

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Costimulation of Chemokine Receptor Signaling by Matrix Metalloproteinase-9 Mediates Enhanced Migration of IFN-α Dendritic Cells

Ivashkiv

2006

The Journal of Immunology

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Type I IFNs induce differentiation of dendritic cells (DCs) with potent Ag-presenting capacity, termed IFN-α DCs, that have been implicated in the pathogenesis of systemic lupus erythematosus. In this study, we found that IFN-α DCs exhibit enhanced migration across the extracellular matrix (ECM) in response to chemokines CCL3 and CCL5 that recruit DCs to inflammatory sites, but not the lymphoid-homing chemokine CCL21. IFN-α DCs expressed elevated matrix metalloproteinase-9 (MMP-9), which mediated increased migration across ECM. Unexpectedly, MMP-9 and its cell surface receptors CD11b and CD44 were required for enhanced CCL5-induced chemotaxis even in the absence of a matrix barrier. MMP-9, CD11b, and CD44 selectively modulated CCL5-dependent activation of JNK that was required for enhanced chemotactic responses. These results establish the migratory phenotype of IFN-α DCs and identify an important role for costimulation of chemotactic responses by synergistic activation of JNK. Thus, cell motility is regulated by integrating signaling inputs from chemokine receptors and molecules such as MMP-9, CD11b, and CD44 that also mediate cell interactions with inflammatory factors and ECM.

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Section: Increased Migration Of Ifn-␣ Dcs Mediated By Ccr5 and Ccr1supporting

confidence: 81%

Section: Increased Migration Of Ifn-␣ Dcs Mediated By Ccr5 and Ccr1mentioning

confidence: 99%

Costimulation of Chemokine Receptor Signaling by Matrix Metalloproteinase-9 Mediates Enhanced Migration of IFN-α Dendritic Cells

Ivashkiv

2006

The Journal of Immunology

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“…IFN-␣ has been recently shown to induce the rapid maturation of monocytes into DCs (IFN-DCs) displaying potent priming activity on virus-specific T lymphocytes and functional characteristics typical of mature cells (12,14,26). This recent knowledge about the interactions between IFN-␣ and DCs has thus opened new perspectives in the use of this cytokine as vaccine adjuvant as well as in strategies for the development of DC-based immunotherapy (12,13).…”

Section: Discussionmentioning

confidence: 99%

Role of Cross-Talk between IFN-α-Induced Monocyte-Derived Dendritic Cells and NK Cells in Priming CD8+ T Cell Responses against Human Tumor Antigens

Tosi¹,

Valenti²,

Cova³

et al. 2004

The Journal of Immunology

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In the present study we evaluated the role of IFN-α in the generation of dendritic cells (IFN-DCs) with priming activity on CD8+ T lymphocytes directed against human tumor Ags. A 3-day treatment of monocytes, obtained as adherent PBMCs from HLA-A*0201+ healthy donors, with IFN-α and GM-CSF led to the differentiation of DCs displaying a semimature phenotype, but promptly inducing CD8+ T cell responses after one in vitro sensitization with peptides derived from melanoma (gp100209–217 and MART-1/Melan-A27–35) and adenocarcinoma (CEA605–613) Ags. However, these features were lost when IFN-DCs were generated from immunosorted CD14+ monocytes. The ability of adherent PBMCs to differentiate into IFN-DCs expressing higher levels of costimulatory molecules and exerting efficient T cell priming capacity was associated with the presence of contaminating NK cells, which underwent phenotypic and functional activation upon IFN-α treatment. NK cell boost appeared to be mediated by both direct and indirect (i.e., mediated by IFN-DCs) mechanisms. Experiments performed to prove the role of contaminating NK cells in DC differentiation showed that IFN-DCs generated in the absence of NK were phenotypically less mature and could not efficiently prime antitumor CD8+ lymphocytes. Reciprocally, IFN-DCs raised from immunosorted CD14+ monocytes regained their T cell priming activity when NK cells were added to the culture before IFN-α and GM-CSF treatment. Together, our data suggest that the ability of IFN-DCs to efficiently prime anti-tumor CD8+ T lymphocytes relied mostly on the positive cross-talk occurring between DCs and NK cells upon stimulation with IFN-α.

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“…In addition, when IL-4-DC are intradermally injected into humans, they show limited migration to LN [47]. IFN-a/b inclusion in clinical-grade cultures has been proposed for production and maturation of DC [28,30], due to the fact that IFN-a (i) enhances crosspriming, (ii) improves the expansion of CTL and (iii) favours DC adhesion/migration properties. We are currently including IFN-a in the DC maturation cultures for an ongoing cancer clinical trial at our institution (NCT00610389), in which we observe in scintigraphic scans more avid migration of DC into LN (I. Melero et al, unpublished results).…”

Section: Aadmentioning

confidence: 99%

“…DC can be differentiated from monocytes (i.e. monocyte-derived DC, MoDC) in the presence of GM-CSF1 IFN-a [30,31] to a cell population named IFN-DC.…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN‐α

et al. 2010

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Migration of DC into lymphatic vessels ferries antigenic cargo and pro-inflammatory stimuli into the draining LN. Given that tissues under the influence of viral infections produce type I IFN, it is conceivable that these cytokines enhance DC migration in order to facilitate an antiviral immune response. Cultured lymphatic endothelium monolayers pretreated with TNF-a were used to model this phenomenon under inflammatory conditions. DC differentiated in the presence of either IFN-a2b or IFN-a5 showed enhanced adhesion to cultured lymphatic endothelial cells. These pro-adhesive effects were mediated by DC, not the lymphatic endothelium, and correlated with increased DC transmigration across lymphatic endothelial cell monolayers. Transmigration was guided by chemokines acting on DC, and blocking experiments with mAb indicated a role for LFA-1. Furthermore, incubation of DC with IFN-a led to the appearance of active conformation epitopes on the CD11a integrin chains expressed by DC. Differentiation of mouse DC in the presence of IFN-a also increased DC migration from inflammed footpads toward popliteal LN. Collectively, these results indicate a role for type I IFN in directing DC toward LN under inflammatory conditions.

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Monocyte-Derived Dendritic Cells Generated After a Short-Term Culture with IFN-α and Granulocyte-Macrophage Colony-Stimulating Factor Stimulate a Potent Epstein-Barr Virus-Specific CD8+ T Cell Response

Cited by 76 publications

References 41 publications

Costimulation of Chemokine Receptor Signaling by Matrix Metalloproteinase-9 Mediates Enhanced Migration of IFN-α Dendritic Cells

Costimulation of Chemokine Receptor Signaling by Matrix Metalloproteinase-9 Mediates Enhanced Migration of IFN-α Dendritic Cells

Role of Cross-Talk between IFN-α-Induced Monocyte-Derived Dendritic Cells and NK Cells in Priming CD8+ T Cell Responses against Human Tumor Antigens

Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN‐α

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