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Efficient stimulation of T cell responses by human IFN-alpha-induced dendritic cells does not require Toll-like receptor triggering

Bracci, L. and Schumacher, R. and Provenzano, M. and Adamina, M. and Rosenthal, R. and Groeper, C. and Zajac, P. and Iezzi, G. and Proietti, E. and Belardelli, F. and Spagnoli, G. C.. (2008) Efficient stimulation of T cell responses by human IFN-alpha-induced dendritic cells does not require Toll-like receptor triggering. Journal of immunotherapy, Vol. 31, H. 5. pp. 466-474.

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Official URL: http://edoc.unibas.ch/dok/A6007159

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Abstract

Dendritic cells (DC) can be activated by proinflammatory cytokines or upon toll-like receptor (TLR) triggering. These stimuli induce specific patterns of phenotypic modulation and gene expression profiles. We investigated whether TLR triggering represents an indispensable requirement for the induction of T cell responses by human DC generated upon culture of monocytes in the presence of granulocyte macrophage colony-stimulating factor and interferon-alpha (IFN-DC). As model stimulator we chose imidazoquinolone (3M-001), a synthetic TLR7 agonist used in the treatment of skin infections and tumors and as experimental adjuvant. At difference with DC generated upon culture of monocytes in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL-4) (IL-4-DC), IFN-DC display a semimature phenotype. Furthermore, IFN-DC, but not IL-4-DC are able to induce CD4+ and CD8+ T cell responses, in steady state, for example, in the absence of TLR triggering. 3M-001 treatment induces up-regulation of the surface expression of costimulatory molecules and "de novo" production of IL-12 and IL-6 in IFN-DC. However, TLR7 triggering fails to significantly enhance the capacity of IFN-DC to induce antigen-specific cytotoxic T lymphocytes and to stimulate allogeneic CD4+ T cells. These data indicate that TLR engagement and IL-12 production do not represent indispensable prerequisites for optimal antigen-presenting cell function in IFN-DC, qualifying these cells as powerful cellular reagents of potential use in active specific immunotherapy.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
UniBasel Contributors:Spagnoli, Giulio C. and Zajac, Paul and Adamina, Michel
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Lippincott Williams & Wilkins
ISSN:1524-9557
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2013 08:29
Deposited On:08 Nov 2013 08:29

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