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.

Nizzoli, G., Krietsch, J., Weick, A., Steinfelder, S., Facciotti, F., Gruarin, P., et al. (2013). Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. BLOOD, 122(6), 932-942 [10.1182/blood-2013-04-495424].

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

NIZZOLI, GIULIA
;
Facciotti, F;BIANCO, ANNALISA;
2013

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.
Articolo in rivista - Articolo scientifico
Animals; Antigen Presentation; Antigens, CD1; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Cell Separation; Cytokines; Dendritic Cells; Glycoproteins; Humans; Immunologic Memory; Interferon-alpha; Interferon-gamma; Interleukin-12; Lymphocyte Activation; Mice; Phenotype; T-Lymphocytes, Cytotoxic; Toll-Like Receptors; Hematology; Biochemistry; Cell Biology; Immunology
English
2013
122
6
932
942
none
Nizzoli, G., Krietsch, J., Weick, A., Steinfelder, S., Facciotti, F., Gruarin, P., et al. (2013). Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses. BLOOD, 122(6), 932-942 [10.1182/blood-2013-04-495424].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/78714
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