Targeting antigens through blood dendritic cell antigen 2 (BDCA2) on plasmacytoid dendritic cells promotes immunologic tolerance1

The C-type lectin receptor blood dendritic cell antigen 2 (BDCA2) is expressed exclusively on human plasmacytoid dendritic cells (pDCs) and plays a role in Ag capture, internalization and presentation to T cells. We used transgenic mice that express human BDCA2 and anti-BDCA2 mAbs to deliver Ags directly to BDCA2 on pDCs in vivo . Targeting Ag to pDCs in this manner resulted in significant suppression of Ag-specific CD4 + T cell and Ab responses upon secondary exposure to Ag in the presence of adjuvant. Suppression of Ab responses required both a decrease in effector CD4 + T cells and preservation of Foxp3 + regulatory T cells (T regs ). Reduction in T reg cell numbers following Ag delivery to BDCA2 restored both CD4 + T cell activation and Ab responses, demonstrating that T regs were required for the observed tolerance. Our results demonstrate that Ag delivery to pDCs through BDCA2 is an effective method to induce immunological tolerance, which may be useful for treating autoimmune diseases or to inhibit unwanted Ab responses.