In situ Delivery of Antigen to DC-SIGN(+)CD14(+) Dermal Dendritic Cells Results in Enhanced CD8(+) T-Cell Responses.
J Invest Dermatol
; 135(9): 2228-2236, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-25885805
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.
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MEDLINE
Asunto principal:
Moléculas de Adhesión Celular
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Presentación de Antígeno
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Receptores de Superficie Celular
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Linfocitos T CD8-positivos
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Receptores de Lipopolisacáridos
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Lectinas Tipo C
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article