TY - JOUR
T1 - Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-α
AU - Della Bella, Silvia
AU - Nicola, Stefania
AU - Riva, Antonio
AU - Biasin, Mara
AU - Clerici, Mario
AU - Villa, Maria Luisa
PY - 2004/1
Y1 - 2004/1
N2 - 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 I 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-α (IFN-DCs). We found that IFN-α 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-α, 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-γ) 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.
AB - 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 I 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-α (IFN-DCs). We found that IFN-α 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-α, 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-γ) 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.
KW - Antigen presenting cells
KW - Cytokines
KW - Th1/Th2
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U2 - 10.1189/jlb.0403154
DO - 10.1189/jlb.0403154
M3 - Article
C2 - 14525963
AN - SCOPUS:0842304585
VL - 75
SP - 106
EP - 116
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -