Abstract
Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4+ T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4+ T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4+ T cells. The generation of such IL-10-producing CD4+ T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4+ T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10- producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.
Original language | English (US) |
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Pages (from-to) | 109-121 |
Number of pages | 13 |
Journal | Journal of Experimental Medicine |
Volume | 209 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2012 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology