title: Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-alpha.
abstract: Monocyte-derived dendritic cells (DCs) generated in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4-DCs) are used to enhance antitumor immunity in cancer patients, although recent evidence suggests that their functional repertoire may be incomplete; in particular, IL-4-DCs appear unable to induce type 2 cytokine-producing T helper (Th) cells. To assess whether type 1 interferon (IFN) could replace IL-4 and generate DCs with a more complete repertoire, we characterized in detail DCs generated from human monocytes cultured with GM-CSF and IFN-alpha (IFN-DCs). We found that IFN-alpha induces DC differentiation more efficiently than IL-4, yielding similar numbers of DCs in a shorter time and that this differentiation persists upon removal of cytokines. Although IFN-DCs had a more mature immunophenotype than IL-4-DCs, showing higher expression of CD80, CD86, and CD83, they still preserved comparable endocytic and phagocytic capacities and responsiveness to maturation stimuli. IFN-DCs had strong antigen-presenting capacity, inducing intense proliferation of T cells to alloantigens or influenza virus. Moreover, IFN-DCs produced lower levels of IL-12p70 and higher levels of IFN-alpha, IL-4, and IL-10 than IL-4-DCs. As a consequence of this different pattern of cytokine secretion, IFN-DCs induced T cells to produce type 1 (IFN-gamma) and type 2 (IL-4 and IL-10) cytokines, and as expected, IL-4-DCs induced only Th1 differentiation. As immune responses with extreme Th1 bias are considered inadequate for the induction of optimal, systemic antitumor immunity, the ability of IFN-DCs to promote more balanced cytokine responses may suggest the advisability to consider these cells in the development of future, DC-based immunotherapy trials.
authors.affiliation: Dipartmento di Scienze e Technologie Biomediche, Cattedra di Immunologia, Università degli Studi di Milano, L.I.T.A., via Fratelli Cervi 93, 20090 Segrate, Milan, Italy. silvia.dellabella@unimi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Bella
authors.forename: Stefania
authors.initials: S
authors.lastname: Nicola
authors.forename: Antonio
authors.initials: A
authors.lastname: Riva
authors.forename: Mara
authors.initials: M
authors.lastname: Biasin
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Villa
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000302:isolation & purification; D003713:Dendritic Cells / Q000145:classification* / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor