First Author | Edgar LJ | Year | 2019 |
Journal | Cell Chem Biol | Volume | 26 |
Issue | 1 | Pages | 131-136.e4 |
PubMed ID | 30393066 | Mgi Jnum | J:286511 |
Mgi Id | MGI:6389965 | Doi | 10.1016/j.chembiol.2018.10.006 |
Citation | Edgar LJ, et al. (2019) Targeted Delivery of Antigen to Activated CD169(+) Macrophages Induces Bias for Expansion of CD8(+) T Cells. Cell Chem Biol 26(1):131-136.e4 |
abstractText | Macrophages (MOs) 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. |