Chen Weimin, Zhang Quanxuan, Kaplan Barbara L F, Baker Gregory L, Kaminski Norbert E
Department of Microbiology and Molecular Genetics .
Nanotoxicology. 2014 Aug;8 Suppl 1:11-23. doi: 10.3109/17435390.2013.848302. Epub 2013 Nov 21.
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 OVA257-264 or OVA323-339, 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.
工程纳米颗粒广泛应用于商业产品中，但由于安全信息匮乏，人们对其潜在的健康不良影响存在担忧，尤其是吸入纳米颗粒及其对过敏性气道疾病的假定影响。本研究的目的是调查工程纳米颗粒的尺寸或表面化学性质是否会影响这些制剂对抗原特异性T细胞反应的免疫增强特性。卵清蛋白（OVA）衍生的肽由脾脏来源的内源性抗原呈递细胞或小鼠树突状细胞（DC）系DC2.4呈递给T细胞。在所有模型中，通过流式细胞术测量CD8(+)或CD4(+) T细胞分别对肽OVA257 - 264或OVA323 - 339产生的干扰素（IFN）-γ和白细胞介素（IL）-2。为了实现研究目标，用炔基封端的表面修饰二氧化硅纳米颗粒（SNP），并通过“点击”化学连接聚乙二醇链。这些修饰的SNP在体外培养基中抗团聚，表明它们对T细胞反应的调节是真正的纳米级介导效应的结果。在次优T细胞活化条件下，修饰的SNP（高达10μg/ml）增加了产生IFN-γ和IL-2的CD8(+) T细胞的比例，但未增加CD4(+) T细胞的比例。修饰的SNP上的各种官能团（-COOH、-NH2和-OH）将IFN-γ和IL-2的产生提高到不同水平，其中-COOH SNP最有效。此外，51nm的-COOH SNP对CD8(+) T细胞反应的增强作用比其他尺寸的颗粒更大。总体而言，我们的结果表明修饰的SNP可以增强抗原特异性CD8(+) T细胞反应，表明某些修饰的SNP具有潜在的佐剂样特性。
