Dendritic cells (DC) have the unique capacities to induce primary T-cell responses. In mice, CD8 alpha+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 CD8 alpha+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-lambda and interferon-alpha, 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.

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses / G. Nizzoli, J. Krietsch, A. Weick, S. Steinfelder, F. Facciotti, P. Gruarin, A. Bianco, B. Steckel, M. Moro, M. Crosti, C. Romagnani, K. Stölzel, S. Torretta, L. Pignataro, C. Scheibenbogen, P. Neddermann, R. De Francesco, S. Abrignani, J. Geginat. - In: BLOOD. - ISSN 0006-4971. - 122:6(2013 Aug), pp. 932-942.

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

G. Nizzoli;S. Torretta;L. Pignataro;R. De Francesco;S. Abrignani;J. Geginat
2013

Abstract

Dendritic cells (DC) have the unique capacities to induce primary T-cell responses. In mice, CD8 alpha+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 CD8 alpha+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-lambda and interferon-alpha, 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.
antigen cross-presentation; inflamed lymph-nodes; in-vivo; presentation capacity; mouse; subsets; CD8(+); activation; helper; blood
Settore MED/31 - Otorinolaringoiatria
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/247612
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