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Virosome-bound antigen enhances DC-dependent specific CD4 + T cell stimulation, inducing a Th1 and Treg profile in vitro


Blom, Rebecca A M; Amacker, Mario; Moser, Christian; van Dijk, R Maarten; Bonetti, Raffaela; Seydoux, Emilie; Hall, Sean R R; von Garnier, Christophe; Blank, Fabian (2017). Virosome-bound antigen enhances DC-dependent specific CD4 + T cell stimulation, inducing a Th1 and Treg profile in vitro. Nanomedicine: Nanotechnology, Biology, and Medicine, 13(5):1725-1737.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:CD4(+) T cells; Immune modulation; Liposomes; Mouse dendritic cells; Virosomes
Language:English
Date:5 July 2017
Deposited On:27 Jun 2017 07:00
Last Modified:02 Jul 2017 05:40
Publisher:Elsevier
ISSN:1549-9634
Publisher DOI:https://doi.org/10.1016/j.nano.2017.02.004
PubMed ID:28214610

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