468
Views
80
CrossRef citations to date
0
Altmetric
Research Article

Biomedical nanoparticles modulate specific CD4+ T cell stimulation by inhibition of antigen processing in dendritic cells

, , , , , , , , , , & show all
Pages 606-621 | Received 23 Aug 2010, Accepted 15 Nov 2010, Published online: 13 Jan 2011
 

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.

Acknowledgements

We gratefully acknowledge the helpful discussions provided by Dr Amiq Gazdhar, critical reading of the manuscript by Dr Phil Stumbles, as well as expert technical assistance provided by Ursula Gerber and Patrizia Castiglioni.

Declaration of interest: Grant-in-aid from the Department of Clinical Research, Bern University Hospital and research grant from the Swiss Society for Pulmonology (CvG), as well as Swiss National Science Foundation Grants No. 320030–122355 (CvG) and No. 205321–120161 (APF). The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.