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In situ Delivery of Antigen to DC-SIGN+CD14+ Dermal Dendritic Cells Results in Enhanced CD8+ T-Cell Responses.
- Source :
-
Journal of Investigative Dermatology . Sep2015, Vol. 135 Issue 9, p2228-2236. 9p. - Publication Year :
- 2015
-
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 LewisX, 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DENDRITIC cells
*MACROPHAGES
*T cells
*INTRADERMAL injections
*LIPOSOMES
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Volume :
- 135
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Investigative Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 108864712
- Full Text :
- https://doi.org/10.1038/jid.2015.152