Targeting antigens through blood dendritic cell antigen 2 on plasmacytoid dendritic cells promotes immunologic tolerance

Craig P. Chappell, Natalia V. Giltiay, Kevin E. Draves, Chang Hung Chen, Martha S. Hayden-Ledbetter, Mark J. Shlomchik, Daniel H. Kaplan, Edward A. Clark

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The C-type lectin receptor blood dendritic cell Ag 2 (BDCA2) is expressed exclusively on human plasmacytoid DCs (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 (Tregs). Reduction in Treg numbers following Ag delivery to BDCA2 restored both CD4+ T cell activation and Ab responses, demonstrating that Tregs 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.

Original languageEnglish (US)
Pages (from-to)5789-5801
Number of pages13
JournalJournal of Immunology
Volume192
Issue number12
DOIs
StatePublished - Jun 15 2014

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