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.

Keywords::

• SPIONs
• dendritic cells
• immune response
• antigen processing
• antigen presentation

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.