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

• Published in: Blood Vol. 122; no. 6; pp. 932 - 942
• Main Authors: Nizzoli, Giulia, Krietsch, Jana, Weick, Anja, Steinfelder, Svenja, Facciotti, Federica, Gruarin, Paola, Bianco, Annalisa, Steckel, Bodo, Moro, Monica, Crosti, Mariacristina, Romagnani, Chiara, Stölzel, Katharina, Torretta, Sara, Pignataro, Lorenzo, Scheibenbogen, Carmen, Neddermann, Petra, De Francesco, Raffaele, Abrignani, Sergio, Geginat, Jens
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08-08-2013
• Subjects: Animals; Antigen Presentation; Antigens, CD1 - metabolism; CD4-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - cytology; Cell Proliferation; Cell Separation; Cytokines - metabolism; Dendritic Cells - cytology; Dendritic Cells - metabolism; Glycoproteins - metabolism; Humans; Immunologic Memory; Interferon-alpha - metabolism; Interferon-gamma - metabolism; Interleukin-12 - metabolism; Lymphocyte Activation; Mice; Phenotype; T-Lymphocytes, Cytotoxic - cytology; Toll-Like Receptors - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-04-495424

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.
•CD1c+ DC but not BDCA-3+ DC or other antigen-presenting cells secrete high amounts of bioactive IL-12.•CD1c+ DC efficiently cross-present antigens, prime CD8+ T cells, and induce the highest levels of cytotoxic molecules.