1. In situ Delivery of Antigen to DC-SIGN + CD14 + Dermal Dendritic Cells Results in Enhanced CD8 + T-Cell Responses
- Author
-
Fehres, Cynthia M., Van Beelen, Astrid J., Bruijns, Sven C M, Ambrosini, Martino, Kalay, Hakan, Van Bloois, Louis, Unger, Wendy W J, Garcia-Vallejo, Juan J., Storm, G, De Gruijl, Tanja D., Van Kooyk, Yvette V., Pharmaceutics, Sub Atmospheric physics and chemistry, Sub Drug targeting, Molecular cell biology and Immunology, Medical oncology laboratory, CCA - Immuno-pathogenesis, Biomaterials Science and Technology, Faculty of Science and Technology, Pharmaceutics, Sub Atmospheric physics and chemistry, and Sub Drug targeting
- Subjects
CD14 ,Lipopolysaccharide Receptors ,Enzyme-Linked Immunosorbent Assay ,Receptors, Cell Surface ,Dermatology ,CD8-Positive T-Lymphocytes ,Major histocompatibility complex ,Biochemistry ,Sampling Studies ,Antigen ,Cell Movement ,Polysaccharides ,Humans ,Cytotoxic T cell ,Lectins, C-Type ,Molecular Biology ,Cells, Cultured ,Medicine(all) ,Analysis of Variance ,Antigen Presentation ,Toll-like receptor ,integumentary system ,biology ,Dendritic Cells ,Cell Biology ,Dendritic cell ,22/4 OA procedure ,Cell biology ,DC-SIGN ,Liposomes ,Immunology ,biology.protein ,Cell Adhesion Molecules ,CD8 - Abstract
CD14(+) dendritic cells (DCs) present in the dermis of human skin represent a large subset of dermal DCs (dDCs) that are considered macrophage-like cells with poor antigen (cross)-presenting capacity and limited migratory potential to the lymph nodes. CD14(+) dDC highly express DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), a receptor containing potent endocytic capacity, facilitating intracellular routing of antigens to major histocompatibility complex I and II (MHC-I andII) loading compartments for the presentation to antigen-specific CD8(+) and CD4(+) T cells. Here we show using a human skin explant model that the in situ targeting of antigens to DC-SIGN using glycan-modified liposomes enhances the antigen-presenting capacity of CD14(+) dDCs. Intradermal vaccination of liposomes modified with the DC-SIGN-targeting glycan Lewis(X), containing melanoma antigens (MART-1 or Gp100), accumulated in CD14(+) dDCs and resulted in enhanced Gp100- or MART-1-specific CD8(+) T-cell responses. Simultaneous intradermal injection of the cytokines GM-CSF and IL-4 as adjuvant enhanced the migration of the skin DCs and increased the expression of DC-SIGN on the CD14(+) and CD1a(+) dDCs. These data demonstrate that human CD14(+) dDCs exhibit potent cross-presenting capacity when targeted in situ through DC-SIGN.
- Published
- 2015