Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines

Tschoep, Katharina; Manning, Thomas C.; Harlin, Helena; George, Christopher B.; Johnson, Melissa D.; Gajewski, Thomas F.

doi:10.1189/jlb.0702352

Cited by 17 publications

(13 citation statements)

References 61 publications

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“…In contrast to VRP-infected DCs, DCs that had been terminally matured with TNF-␣ or LPS did not secrete significant levels of IFN-␣, TNF-␣, IL-6, or IL-12p70. This observation is in line with other publications describing the inability of fully matured DCs to secrete several proinflammatory cytokines (56,57). In summary, VRPs represent a novel strategy to deliver TAAs and a strong maturation signal simultaneously to human DCs.…”

Section: Discussionsupporting

confidence: 93%

A Novel Viral System for Generating Antigen-Specific T Cells

Moran¹,

Collier²,

McKinnon

et al. 2005

The Journal of Immunology

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Dendritic cell (DC)-based vaccines are increasingly used for the treatment of patients with malignancies. Although these vaccines are typically safe, consistent and lasting generation of tumor-specific immunity has been rarely demonstrated. Improved methods for delivering tumor Ags to DCs and approaches for overcoming tolerance or immune suppression to self-Ags are critical for improving immunotherapy. Viral vectors may address both of these issues, as they can be used to deliver intact tumor Ags to DCs, and have been shown to inhibit the suppression mediated by CD4+CD25+ regulatory T cells. We have evaluated the potential use of Venezuelan equine encephalitis virus replicon particles (VRPs) for in vitro Ag delivery to human monocyte-derived DCs. VRPs efficiently transduced immature human DCs in vitro, with ∼50% of immature DCs expressing a vector-driven Ag at 12 h postinfection. VRP infection of immature DCs was superior to TNF-α treatment at inducing phenotypic maturation of DCs, and was comparable to LPS stimulation. Additionally, VRP-infected DC cultures secreted substantial amounts of the proinflammatory cytokines IL-6, TNF-α, and IFN-α. Finally, DCs transduced with a VRP encoding the influenza matrix protein (FMP) stimulated 50% greater expansion of FMP-specific CD8+ CTL when compared with TNF-α-matured DCs pulsed with an HLA-A*0201-restricted FMP peptide. Thus, VRPs can be used to deliver Ags to DCs resulting in potent stimulation of Ag-specific CTL. These findings provide the rationale for future studies evaluating the efficacy of VRP-transduced DCs for tumor immunotherapy.

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Section: Discussionsupporting

confidence: 93%

A Novel Viral System for Generating Antigen-Specific T Cells

Moran¹,

Collier²,

McKinnon

et al. 2005

The Journal of Immunology

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“…Because TLR9 mRNA expression was reduced for splenic DCs cultured with medium alone, it may be that the down-regulation of TLRs is related to the maturation of DCs. Such a phenomenon has been previously observed with human monocyte-derived DCs (49,50). In contrast, LPS stimulation has been shown to up-regulate expression of TLR2 or TLR9 by human or mouse macrophages, respectively (51,52).…”

Section: Discussionsupporting

confidence: 58%

Dendritic Cells Derived from Murine Colonic Mucosa Have Unique Functional and Phenotypic Characteristics

Takenaka

Safroneeva

Xing

et al. 2007

The Journal of Immunology

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Dendritic cells (DCs) residing in different tissues and exposed to different organisms are likely to have different reactivities to their surrounding environment. Many studies use in vitro generated DCs to examine functions of these cells, but such cells may not truly reflect the nature of DCs and their in situ activities in vivo. We have used magnetic label-based technique to isolate colonic DCs to conduct derailed characterization of these cells. Colonic DCs comprise mainly CD11b+ DCs with few CD8α+ DCs or plasmacytoid DCs. Functionally, isolated colonic DCs are able to endocytose and process proteins, undergo maturation, and stimulate T cells to proliferate. Importantly, expression of TLRs by colonic DCs is significantly lower than that of their spleen counterparts; however, they appear to be as, or more, responsive to stimulation by oligodeoxynucleotides containing CpG motif based on their cytokine production. We speculate that colonic DCs have unique reactivities differing from DCs residing in other lymphoid tissues and are adapted for the unique microenvironment of the colonic mucosa and that these cells react uniquely to their environment.

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“…One of the main subsets are myeloid DC (mDC), characterized by CD11c + and CD123 -, which pick up antigens in the periphery and trigger immunity after migration to lymphoid organs. Depending on the antigen and other factors, mDC are capable to induce a Th1 or a Th2 cytokine pattern [12] .…”

Section: Introductionmentioning

confidence: 99%

Histamine Downregulates the Th1-Associated Chemokine IP-10 in Monocytes and Myeloid Dendritic Cells

Glatzer

Mommert²,

Köther³

et al. 2013

Int Arch Allergy Immunol

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fect was mediated via H 2 R and H 4 R in monocytes and mDC. Conclusion: Monocytes and mDC have similar histamine receptor repertoires with regard to H 1 R, H 2 R and H 3 R, but H 4 R expression is higher on mDC. Histamine stimulation shows similar functional effects on both cell types, i.e., downregulation of TLR3-induced IP-10 production. This might be a new mechanism how histamine fosters a Th2 milieu.

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Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines

Cited by 17 publications

References 61 publications

A Novel Viral System for Generating Antigen-Specific T Cells

A Novel Viral System for Generating Antigen-Specific T Cells

Dendritic Cells Derived from Murine Colonic Mucosa Have Unique Functional and Phenotypic Characteristics

Histamine Downregulates the Th1-Associated Chemokine IP-10 in Monocytes and Myeloid Dendritic Cells

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