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.

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