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Prostaglandin E(2) in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8(+) T cells
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covidontheweb.inria.fr
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Prostaglandin E(2) in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8(+) T cells
Creator
Eyrich, Matthias
Wölfl, Matthias
Sauer, Sascha
Gierlich, Philipp
Glunz, Amelie
Grigoleit, Ulrich
Götz, ·
Hanno Sennholz, ·
Keupp, Anne
Lex, Veronika
Lorenz Morper, ·
Marcu, Ana
Rachor, Johannes
Schlegel, Paul
Technau, Antje
Source
PMC
abstract
Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E(2) (PGE(2)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8(+) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8(+) T-cells from naïve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8(+) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE(2) during DC maturation and reproducible with several responder T-cell lines. In conclusion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE(2) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02470-1) contains supplementary material, which is available to authorized users.
has issue date
2020-02-25
(
xsd:dateTime
)
bibo:doi
10.1007/s00262-019-02470-1
bibo:pmid
32100075
has license
no-cc
sha1sum (hex)
3ef29f84d7ef41650dc1df3e9c5faf64d12029db
schema:url
https://doi.org/10.1007/s00262-019-02470-1
resource representing a document's title
Prostaglandin E(2) in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8(+) T cells
has PubMed Central identifier
PMC7223547
has PubMed identifier
32100075
schema:publication
Cancer Immunol Immunother
resource representing a document's body
covid:3ef29f84d7ef41650dc1df3e9c5faf64d12029db#body_text
is
schema:about
of
named entity 'T-cells'
named entity 'specific'
named entity 'optimal'
named entity 'complex'
named entity 'represent'
named entity 'long'
named entity 'T-cell'
named entity 'protein'
named entity 'DCs'
named entity 'cocktail'
named entity 'TLR3'
named entity 'generates'
named entity 'ANTIGENS'
named entity 'MATURATION'
named entity 'CAPABILITY'
named entity 'IL-1'
named entity 'DCs'
named entity 'primed'
named entity 'antigens'
named entity 'dendritic cells'
named entity 'migration'
named entity 'standard'
named entity 'integrin'
named entity 'cancer vaccines'
named entity 'combination'
named entity 'PTP'
named entity 'activation'
named entity 'DCs'
named entity 'proteins'
named entity 'T cells'
named entity 'CD8 +'
named entity 'IL-8'
named entity 'CD83'
named entity 'dose-dependent'
named entity 'CD80'
named entity 'TLR'
named entity 'agonists'
named entity 'TLR'
named entity 'DCs'
named entity 'antigens'
named entity 'TLR'
named entity 'DCs'
named entity 'DCs'
named entity 'proinflammatory cytokines'
named entity 'TLR'
named entity 'NLGN4X'
named entity 'IL-6'
named entity 'Secretion'
named entity 'CDCs'
named entity 'PTP'
named entity 'TLR3'
named entity 'cross-presentation'
named entity 'CD8 +'
named entity 'proinflammatory cytokines'
named entity 'cytokine'
named entity 'TLR'
named entity 'tyrosine'
named entity 'imiquimod'
named entity 'DCs'
named entity 'organism'
named entity 'APC'
named entity 'CD3'
named entity 'IFNγ'
named entity 'cancer vaccine'
named entity 'DCs'
named entity 'phenotype'
named entity 'intracellular'
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