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Cell Chem Biol. 2019 Jan 17;26(1):131-136.e4. doi: 10.1016/j.chembiol.2018.10.006. Epub 2018 Nov 1.

Targeted Delivery of Antigen to Activated CD169+ Macrophages Induces Bias for Expansion of CD8+ T Cells.

Author information

1
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jpaulson@scripps.edu.

Abstract

Macrophages (MØs) expressing the endocytic sialic acid-binding immunoglobulin-like lectin 1 (siglec-1, CD169, sialoadhesin) are known to be adept at antigen capture-primarily due to their strategic location within lymphatic tissues. Antigen concentrated in these cells can be harnessed to induce potent anti-tumor/anti-pathogen cytotoxic (CD8+) T cell responses. Here, we describe a chemical platform that exploits the CD169-mediated antigen capture pathway for biased priming of antigen-specific CD4+ or CD8+ T cells in vivo. In the absence of a toll-like receptor (TLR) agonist, antigen delivery through CD169 produced robust CD4+ T cell priming only. However, simultaneous treatment with targeted antigen and a TLR7 agonist induced CD8+ T cell priming, with concomitant suppression of the CD4+ T cell response. We exploited these observations to manipulate the activation ratio of CD4+/CD8+ T cells in the same animal. These findings represent a unique chemical strategy for targeting CD169+ macrophages to modulate antigen-specific T cell immunity.

KEYWORDS:

T cell; antigen-presentation; glycans; immunity; liposome-targeting; macrophage; siglec-1

PMID:
30393066
PMCID:
PMC6338492
[Available on 2020-01-17]
DOI:
10.1016/j.chembiol.2018.10.006

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