title: Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells.
abstract: Understanding how nanoparticles may affect immune responses is an essential prerequisite to developing novel clinical applications. To investigate nanoparticle-dependent outcomes on immune responses, dendritic cells (DCs) were treated with model biomedical poly(vinylalcohol)-coated super-paramagnetic iron oxide nanoparticles (PVA-SPIONs). PVA-SPIONs uptake by human monocyte-derived DCs (MDDCs) was analyzed by flow cytometry (FACS) and advanced imaging techniques. Viability, activation, function, and stimulatory capacity of MDDCs were assessed by FACS and an in vitro CD4+ T cell assay. PVA-SPION uptake was dose-dependent, decreased by lipopolysaccharide (LPS)-induced MDDC maturation at higher particle concentrations, and was inhibited by cytochalasin D pre-treatment. PVA-SPIONs did not alter surface marker expression (CD80, CD83, CD86, myeloid/plasmacytoid DC markers) or antigen-uptake, but decreased the capacity of MDDCs to process antigen, stimulate CD4+ T cells, and induce cytokines. The decreased antigen processing and CD4+ T cell stimulation capability of MDDCs following PVA-SPION treatment suggests that MDDCs may revert to a more functionally immature state following particle exposure.
authors.affiliation: Department of Clinical Research , Division of Pulmonology, Bern University Hospital, Bern, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
authors.forename: Peter
authors.initials: P
authors.lastname: Gerber
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
authors.forename: Usawadee
authors.initials: U
authors.lastname: Sakulkhu
authors.forename: Jatuporn
authors.initials: J
authors.lastname: Salaklang
authors.forename: Karin
authors.initials: K
authors.lastname: De Peyer
authors.forename: Peter
authors.initials: P
authors.lastname: Gehr
authors.forename: Laurent P
authors.initials: LP
authors.lastname: Nicod
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hofmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Geiser
authors.forename: Alke
authors.initials: A
authors.lastname: Petri-Fink
authors.forename: Christophe
authors.initials: C
authors.lastname: Von Garnier
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D058185:Magnetite Nanoparticles / Q000737:chemistry*
chemical_list: D005290:Ferric Compounds; D006681:HLA-D Antigens; D008070:Lipopolysaccharides; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D015638:Cytochalasin D