title: Virosome-bound antigen enhances DC-dependent specific CD4+T cell stimulation, inducing a Th1 and Treg profile in vitro.
abstract: There is considerable interest to develop antigen-carriers for immune-modulatory clinical applications, but insufficient information is available on their effects on antigen-presenting cells. We employed virosomes coupled to ovalbumin (OVA) to study their interaction with murine bone marrow-derived dendritic cells (BMDCs) and modulation of downstream T cell responses. BMDCs were treated in vitro with virosomes or liposomes prior to determining BMDC phenotype, viability, and intracellular trafficking. Antigen-specific CD4+T cell activation was measured by co-culture of BMDCs with DO11.10 CD4+T cells. Compared to liposomes, virosomes were rapidly taken up. Neither nanocarrier type affected BMDC viability, nor did a moderate degree of activation differ for markers such as CD40, CD80, CD86. Virosome uptake occurred via clathrin-mediated endocytosis and phagocytosis, with co-localization in late endosomes. Only BMDCs treated with OVA-coupled virosomes induced enhanced OVA-specific CD4+T cell proliferation. Antigen-coupled virosomes are endowed with an intrinsic ability to modulate DC-dependent adaptive immune responses.
authors.affiliation: Department of Pulmonary Medicine, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Rebecca A M
authors.initials: RAM
authors.lastname: Blom
authors.affiliation: Mymetics SA, Epalinges, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Amacker
authors.affiliation: Swiss Federal Institute of Intellectual Property, Bern, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Moser
authors.affiliation: Institute of Anatomy, University of Zürich, Switzerland; Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
authors.forename: R Maarten
authors.initials: RM
authors.lastname: van Dijk
authors.affiliation: Department of Pulmonary Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Bonetti
authors.affiliation: Department of Pulmonary Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Seydoux
authors.affiliation: Division of Thoracic Surgery, University Hospital of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Sean R R
authors.initials: SRR
authors.lastname: Hall
authors.affiliation: Department of Pulmonary Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.affiliation: Department of Pulmonary Medicine, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: fabian.blank@dkf.unibe.ch.
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000941:Antigens; D015496:CD4-Positive T-Lymphocytes; D003713:Dendritic Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D050378:T-Lymphocytes, Regulatory; D018417:Th1 Cells; D022701:Virosomes
chemical_list: D000941:Antigens; D022701:Virosomes; D010047:Ovalbumin
keywords: CD4(+) T cells; Immune modulation; Liposomes; Mouse dendritic cells; Virosomes