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

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. and Krietsch, J. and Weick, A. and Steinfelder, S. and Facciotti, F. and Gruarin, P. and Bianco, A. and Steckel, B. and Moro, M. and Crosti, M. and Romagnani, C. and Stölzel, K. and Torretta, S. and Pignataro, L. and Scheibenbogen, C. and Neddermann, P. and De Francesco, R. and 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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