Induced T cell cytokine production is enhanced by engineered nanoparticles

Abstract

Engineered nanoparticles are widely used in commercial products, and yet due to the paucity of safety information, there are concerns surrounding potential adverse health effects, especially from inhaled nanoparticles and their putative contribution to allergic airway disease. The objective of this study was to investigate whether size or surface chemistry of engineered nanoparticles can influence the immune enhancing properties of these agents on antigen-specific T cell responses. Ovalbumin (OVA)-derived peptides were presented to T cells by either spleen-derived endogenous antigen presenting cells or a mouse dendritic cell (DC) line, DC2.4. In all models, interferon (IFN)-γ and interleukin (IL)-2 production by CD8⁺ or CD4⁺ T cells in response to peptide OVA_257–264 or OVA_323–339, respectively, was measured by flow cytometry. To address the study objective, silica nanoparticles (SNPs) were modified with alkyne-terminated surfaces and appended with polyethylene glycol chains via “click” chemistry. These modified SNPs were resistant to agglomerate in in vitro culture media, suggesting that their modulation of T cell responses is the result of true nanoscale-mediated effects. Under conditions of suboptimal T-cell activation, modified SNPs (up to 10 µg/ml) enhanced the proportion of CD8⁺, but not CD4⁺, T cells producing IFN-γ and IL-2. Various functional groups (–COOH, –NH₂ and –OH) on modified SNPs enhanced IFN-γ and IL-2 production to different levels, with –COOH SNPs being the most effective. Furthermore, 51 nm –COOH SNPs exhibited a greater enhancing effect on the CD8⁺ T cell response than other sized particles. Collectively, our results show that modified SNPs can enhance antigen-specific CD8⁺ T cell responses, suggesting that certain modified SNPs exhibit potential adjuvant-like properties.

• Silica nanoparticles
• cytokines
• T cells
• ovalbumin antigens
• adjuvant

Acknowledgements

The authors would like to thank Mr Robert Crawford for flow cytometric analysis.

Declaration of Interest

The authors declare that they have no competing interests. This work is funded by National Institutes of Health Grant RC2 ES018756.

Authors’ contributions

W. C. designed and performed experiments, analyzed the data and wrote the manuscript. Q. Z. synthesized and characterized the particles and contributed to writing the associated sections. B. L. F. K. and G. L. B. helped design the study and reviewed the manuscript. N. E. K. designed the study, oversaw all experimental work and edited the manuscript. All of the authors have read and approved the final manuscript.