Harnessing human plasmacytoid dendritic cells as professional APCs

Tel, Jurjen; Leun, Anne M. van der; Figdor, Carl G.; Torensma, Ruurd; Vries, I. Jolanda M. de

doi:10.1007/s00262-012-1210-z

Cited by 56 publications

(47 citation statements)

References 81 publications

(96 reference statements)

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“…2 DCs are capable of cross-presentation (51)(52)(53) and that activation of pDCs can enhance CD8 + T cell responses by improving conventional DC functions (33). Collectively, these observations may have implications for vaccine design.…”

Section: Cd8amentioning

confidence: 99%

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Osmond

Farrand

Painter

et al. 2015

The Journal of Immunology

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The function of dendritic cells (DCs) can be modulated through multiple signals, including recognition of pathogen-associated molecular patterns, as well as signals provided by rapidly activated leukocytes in the local environment, such as innate-like T cells. In this article, we addressed the possibility that the roles of different murine DC subsets in cross-priming CD8+ T cells can change with the nature and timing of activatory stimuli. We show that CD8α+ DCs play a critical role in cross-priming CD8+ T cell responses to circulating proteins that enter the spleen in close temporal association with ligands for TLRs and/or compounds that activate NKT cells. However, if NKT cells are activated first, then CD8α− DCs become conditioned to respond more vigorously to TLR ligation, and if triggered directly, these cells can also contribute to priming of CD8+ T cell responses. In fact, the initial activation of NKT cells can condition multiple DC subsets to respond more effectively to TLR ligation, with plasmacytoid DCs making more IFN-α and both CD8α+ and CD8α− DCs manufacturing more IL-12. These results suggest that different DC subsets can contribute to T cell priming if provided appropriately phased activatory stimuli, an observation that could be factored into the design of more effective vaccines.

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Section: Cd8amentioning

confidence: 99%

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Osmond

Farrand

Painter

et al. 2015

The Journal of Immunology

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“…While pDCs may not be the default type of DC to drive T cell responses, activation by the right stimulus results in maturation of pDCs that enables strong T cell activation, which may be employed for immunotherapy [56].…”

Section: Human Dcsmentioning

confidence: 99%

The activation of the adaptive immune system: Cross-talk between antigen-presenting cells, T cells and B cells

2014

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“…Harnessing pDCs for DC-based immunotherapy by direct targeting of pDCs in vivo is an attractive opportunity; it allows the delivery of Ags without extensive handling and ex vivo culturing (16,17). The potency of harnessing pDCs in vivo was already demonstrated in mice, where targeting the murine pDC-specific receptor Siglec-H induced the priming of Ag-specific CD8 + T cells upon Ag uptake via this receptor (18).…”

mentioning

confidence: 99%

Targeting Uptake Receptors on Human Plasmacytoid Dendritic Cells Triggers Antigen Cross-Presentation and Robust Type I IFN Secretion

Tel

Sittig

Blom

et al. 2013

The Journal of Immunology

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101

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Plasmacytoid dendritic cells (pDCs) play a crucial role in initiating immune responses by secreting large amounts of type I IFNs. Currently, the role for human pDCs as professional APCs in the cross-presentation of exogenous Ags is being re-evaluated. Human pDCs are equipped with a broad repertoire of Ag uptake receptors and an efficient Ag-processing machinery. In this study, we set out to investigate which receptor can best be deployed to deliver Ag to pDCs for Ag (cross-)presentation. We show that targeting nanoparticles to pDCs via the C-type lectins DEC-205, DC immunoreceptor, blood DC Ag-2, or the FcR CD32 led to uptake, processing, and (cross-) presentation of encapsulated Ag to both CD4+ and CD8+ T cells. This makes these receptors good candidates for potential in vivo targeting of pDCs by nanocarriers. Notably, the coencapsulated TLR7 agonist R848 efficiently activated pDCs, resulting in phenotypical maturation as well as robust IFN-α and TNF-α production. Taken together, their cross-presentation capacity and type I IFN production to further activate components of both the innate and adaptive immune system mark pDCs as inducers of potent antitumor responses. These findings pave the way to actively recruit human pDCs for cellular cancer immunotherapy.

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Harnessing human plasmacytoid dendritic cells as professional APCs

Cited by 56 publications

References 81 publications

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

The activation of the adaptive immune system: Cross-talk between antigen-presenting cells, T cells and B cells

Targeting Uptake Receptors on Human Plasmacytoid Dendritic Cells Triggers Antigen Cross-Presentation and Robust Type I IFN Secretion

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