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Exploiting the Role of Endogenous Lymphoid-Resident Dendritic Cells in the Priming of NKT Cells and CD8+ T Cells to Dendritic Cell-Based Vaccines
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Exploiting the Role of Endogenous Lymphoid-Resident Dendritic Cells in the Priming of NKT Cells and CD8+ T Cells to Dendritic Cell-Based Vaccines
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Journal Article
Exploiting the Role of Endogenous Lymphoid-Resident Dendritic Cells in the Priming of NKT Cells and CD8+ T Cells to Dendritic Cell-Based Vaccines
2011
Overview
Transfer of antigen between antigen-presenting cells (APCs) is potentially a physiologically relevant mechanism to spread antigen to cells with specialized stimulatory functions. Here we show that specific CD8+ T cell responses induced in response to intravenous administration of antigen-loaded bone marrow-derived dendritic cells (BM-DCs), were ablated in mice selectively depleted of endogenous lymphoid-resident langerin+ CD8α+ dendritic cells (DCs), suggesting that the antigen is transferred from the injected cells to resident APCs. In contrast, antigen-specific CD4+ T cells were primed predominantly by the injected BM-DCs, with only very weak contribution of resident APCs. Crucially, resident langerin+ CD8α+ DCs only contributed to the priming of CD8+ T cells in the presence of maturation stimuli such as intravenous injection of TLR ligands, or by loading the BM-DCs with the glycolipid α-galactosylceramide (α-GalCer) to recruit the adjuvant activity of activated invariant natural killer-like T (iNKT) cells. In fact, injection of α-GalCer-loaded CD1d-/- BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs. While iNKT cell activation per se was independent of langerin+ CD8α+ DCs, some iNKT cell-mediated activities were reduced, notably release of IL-12p70 and transactivation of NK cells. We conclude that both protein and glycolipid antigens can be exchanged between distinct DC species. These data suggest that the efficacy of DC-based vaccination strategies may be improved by the incorporation of a systemic maturation signal aimed to engage resident APCs in CD8+ T cell priming, and α-GalCer may be particularly well suited to this purpose.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antigen-Presenting Cells - cytology
/ Antigen-Presenting Cells - immunology
/ Antigens
/ Antigens, Surface - genetics
/ Antigens, Surface - metabolism
/ Biology
/ Bone Marrow Cells - cytology
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ Dendritic Cells - immunology
/ Killer Cells, Natural - cytology
/ Killer Cells, Natural - immunology
/ Lectins, C-Type - metabolism
/ Lymphoid Tissue - immunology
/ Mannose-Binding Lectins - genetics
/ Mannose-Binding Lectins - metabolism
/ Mice
/ Priming
/ Proteins
/ T cells
/ Vaccines
