Human CD1c(+) dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses

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Item Type:	Article
Title:	Human CD1c(+) dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses
Creators Name:	Nizzoli, G., Krietsch, J., Weick, A., Steinfelder, S., Facciotti, F., Gruarin, P., Bianco, A., Steckel, B., Moro, M., Crosti, M., Romagnani, C., Stölzel, K., Torretta, S., Pignataro, L., Scheibenbogen, C., Neddermann, P., De Francesco, R., Abrignani, S. and Geginat, J.
Abstract:	Dendritic cells (DC) have the unique capacities to induce primary T-cell responses. In mice, CD8α(+)DC are specialized to cross-prime CD8(+) T cells and produce interleukin-12 (IL-12) that promotes cytotoxicity. Human BDCA-3(+)DC share several relevant characteristics with CD8α(+)DC, but the capacities of human DC subsets to induce CD8(+) T-cell responses are incompletely understood. Here we compared CD1c(+) myeloid DC (mDC)1, BDCA-3(+)mDC2, and plasmacytoid DC (pDC) in peripheral blood and lymphoid tissues for phenotype, cytokine production, and their capacities to prime cytotoxic T cells. mDC1 were surprisingly the only human DC that secreted high amounts of IL-12p70, but they required combinational Toll-like receptor (TLR) stimulation. mDC2 and pDC produced interferon-λ and interferon-α, respectively. Importantly, mDC1 and mDC2 required different combinations of TLR ligands to cross-present protein antigens to CD8(+) T cells. pDC were inefficient and also expressed lower levels of major histocompatibility complex and co-stimulatory molecules. Nevertheless, all DC induced CD8(+) memory T-cell expansions upon licensing by CD4(+) T cells, and primed naive CD8(+) T cells following appropriate TLR stimulation. However, because mDC1 produced IL-12, they induced the highest levels of cytotoxic molecules. In conclusion, CD1c(+)mDC1 are the relevant source of IL-12 for naive T cells and are fully equipped to cross-prime cytotoxic T-cell responses.
Keywords:	Antigen Presentation, CD1 Antigens, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Cell Separation, Cytokines, Cytotoxic T-Lymphocytes, Dendritic Cells, Glycoproteins, Immunologic Memory, Interferon-Alpha, Interferon-Gamma, Interleukin-12, Lymphocyte Activation, Phenotype, Toll-Like Receptors, Animals, Mice
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	122
Number:	6
Page Range:	932-942
Date:	8 August 2013
Official Publication:	https://doi.org/10.1182/blood-2013-04-495424
PubMed:	View item in PubMed

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