Selective Activation of Antigen-Experienced T Cells by Anti-CD3 Constrained on Nanoparticles

The Journal of Immunology: Official Journal of the American Association of Immunologists

Michael A. Edidin¹  Jonathan D. Powell³  Ying-Chun Lo⁵ 

[1] and;Department of Biology, Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21231;Department of Materials Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21231;Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21231

DOI  :  10.4049/jimmunol.1301433

学科分类：生物科学（综合）

来源: American Association of Immunologists

【 摘 要 】

Activation of T cells through the TCR is mediated by the TCR-CD3 signaling complex. Cross linking of this complex with Abs directed against CD3 leads to potent activation of T cells. However, such activation is not Ag-specific. We exploited the observation that the TCR-CD3 complex is clustered on T cells that have been activated by Ag by using anti-CD3 nanoparticles to selectively activate Ag-experienced mouse T cells. We find that constraining anti-CD3 on the surface of a nanoparticle markedly and selectively enhances proliferation and cytokine production of Ag-experienced T cells but does not activate naive T cells. This effect was recapitulated in heterogeneous cultures containing mixtures of Ag-specific CD4+ or CD8+ T cells and bystander T cells. Furthermore, in vivo anti-CD3–coated nanoparticles increased the expansion of Ag-specific T cells following vaccination. Overall, these findings indicate that anti-CD3–coated nanoparticles could be use to enhance the efficacy of vaccines and immunotherapy. The results also suggest constraining a ligand on the surface of a nanoparticle might as general strategy for selectively targeting clustered receptors.

【 授权许可】

CC BY