Targeting antigens through blood dendritic cell antigen 2 on plasmacytoid dendritic cells promotes immunologic tolerance.
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.
Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA.
Craig P
CP
Chappell
Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA.
Natalia V
NV
Giltiay
Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA.
Kevin E
KE
Draves
ElAb Bio, Gaithersburg MD.
ChangHung
C
Chen
Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA.
Martha S
MS
Hayden-Ledbetter
Department of Immunology, School of Medicine, University of Pittsburg, Pittsburg, PA, USA.
Mark J
MJ
Shlomchik
Department of Dermatology, University of Minnesota Medical School, Minneapolis, MN, USA.
Daniel H
DH
Kaplan
Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA.|Department of Microbiology, School of Medicine, University of Washington, Seattle, WA, USA.
Edward A
EA
Clark
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
C443299:CLEC4C protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic