title: IFN-alpha-conditioned dendritic cells are highly efficient in inducing cross-priming CD8(+) T cells against exogenous viral antigens.
abstract: Dendritic cells (DC) generated after a short-term exposure of monocytes to IFN-alpha and GM-CSF (IFN-DC) are highly effective in inducing cross-priming of CD8(+ )T cells against viral antigens. We have investigated the mechanisms responsible for the special attitude of these DC and compared their activity with that of reference DC. Antigen uptake and endosomal processing capabilities were similar for IFN-DC and IL-4-derived DC. Both DC types efficiently cross-presented soluble HCV NS3 protein to the specific CD8(+) T cell clone, even though IFN-DC were superior in cross-presenting low amounts of viral antigens. Moreover, when DC were pulsed with inactivated HIV-1 and injected into hu-PBL-SCID mice, the generation of virus-specific CD8(+ )T cells was markedly higher in animals immunized with IFN-DC than in mice immunized with CD40L-matured IL-4-DC. Of interest, in experiments with purified CD8(+ )T cells, IFN-DC were superior with respect to CD40L-matured IL-4-DC in inducing in vitro cross-priming of HIV-specific CD8(+ )T cells. This property correlated with enhanced potential to express the specific subunits of the IL-23 and IL-27 cytokines. These results suggest that IFN-DC are directly licensed for an efficient CD8(+) T cell priming by mechanisms likely involving enhanced antigen presentation and special attitude to produce IL-12 family cytokines.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Lapenta
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Santini
authors.forename: Massimo
authors.initials: M
authors.lastname: Spada
authors.forename: Simona
authors.initials: S
authors.lastname: Donati
authors.forename: Francesca
authors.initials: F
authors.lastname: Urbani
authors.forename: Daniele
authors.initials: D
authors.lastname: Accapezzato
authors.forename: Debora
authors.initials: D
authors.lastname: Franceschini
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011992:Endosomes / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D012995:Solubility; D013997:Time Factors
chemical_list: D000956:Antigens, Viral; D016898:Interferon-alpha; D007378:Interleukins; D023201:CD40 Ligand