Blom, Rebecca Agaatha Maria; Amacker, Mario; Moser, Christian; van Dijk, R Maarten; Bonetti, Raffaela; Seydoux, Emilie; Hall, Sean; 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), pp. 1725-1737. Elsevier 10.1016/j.nano.2017.02.004
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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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