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

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.