Vis, B, Hewitt, RE, Faria, N et al. (6 more authors) (2018) Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells. ACS Nano, 12 (11). pp. 10843-10854. ISSN 1936-0851
Abstract
Sub-micron-sized silica nanoparticles, even as small as 10–20 nm in diameter, are well-known for their activation of mononuclear phagocytes. In contrast, the cellular impact of those <10 nm [i.e., ultrasmall silica nanoparticles (USSN)] is not well-established for any cell type despite anticipated human exposure. Here, we synthesized discrete populations of USSN with volume median diameters between 1.8 to 16 nm and investigated their impact on the mixed cell population of human primary peripheral mononuclear cells. USSN 1.8–7.6 nm in diameter, optimally 3.6–5.1 nm in diameter, induced dose-dependent CD4 and CD8 T-cell activation in terms of cell surface CD25 and CD69 up-regulation at concentrations above 150 μM Sitotal (∼500 nM particles). Induced activation with only ∼2.4 μM particles was (a) equivalent to that observed with typical positive control levels of Staphylococcal enterotoxin B (SEB) and (b) evident in antigen presenting cell-deplete cultures as well as in a pure T-cell line (Jurkat) culture. In the primary mixed-cell population, USSN induced IFN-γ secretion but failed to induce T-cell proliferation or the secretion of IL-2, IL-10, or IL-4. Collectively, these data indicate that USSN initiate activation, with Th1 polarization, of T cells via direct particle–cell interaction. Finally, similarly sized iron hydroxide particles did not induce the expression of T-cell activation markers, indicating some selectivity of the ultrasmall particle type. Given that humans may be exposed to ultrasmall particles and that these materials have emerging bioclinical applications, their off-target immunomodulatory effects via direct T-cell activation should be carefully considered.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 American Chemical Society. This is an author produced version of a paper published in ACS Nano. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | activation; CD25; CD69; nanoparticles; silica; T cells; ultrasmall |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) > FSN Colloids and Food Processing (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Dec 2018 11:17 |
Last Modified: | 22 Oct 2019 00:39 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acsnano.8b03363 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:139449 |