CD28
细胞生物学
T细胞
外域
细胞因子
肿瘤坏死因子α
T细胞受体
材料科学
化学
生物
受体
免疫学
免疫系统
生物化学
作者
Joosung Oh,X.-G. Xia,Wendy H. Wong,Siu Hong Dexter Wong,Weihao Yuan,Shuangfeng Wang,Chun Him Nathanael Lai,Ye Tian,Yi‐Ping Ho,Honglu Zhang,Yuan Zhang,Gang Li,Lin Ye,Liming Bian
出处
期刊:Small
[Wiley]
日期:2022-03-16
卷期号:18 (36)
被引量:16
标识
DOI:10.1002/smll.202107373
摘要
The mechanism of extracellular ligand nano-geometry in ex vivo T cell activation for immunotherapy remains elusive. Herein, the authors demonstrate large aspect ratio (AR) of gold nanorods (AuNRs) conjugated on cell culture substrate enhancing both murine and human T cell activation through the nanoscale anisotropic presentation of stimulatory ligands (anti-CD3(αCD3) and anti-CD28(αCD28) antibodies). AuNRs with large AR bearing αCD3 and αCD28 antibodies significantly promote T cell expansion and key cytokine secretion including interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). High membrane tension observed in large AR AuNRs regulates actin filament and focal adhesion assembly and develops maturation-related morphological features in T cells such as membrane ruffle formation, cell spreading, and large T cell receptor (TCR) cluster formation. Anisotropic stimulatory ligand presentation promotes differentiation of naïve CD8+ T cells toward the effector phenotype inducing CD137 expression upon co-culture with human cervical carcinoma. The findings suggest the importance of manipulating extracellular ligand nano-geometry in optimizing T cell behaviors to enhance therapeutic outcomes.
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