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Published online before print October 2, 2003

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0403154

Received for publication April 16, 2003.
Revised September 1, 2003.
Accepted for publication September 2, 2003.

RA

Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-

Silvia Della Bella ^*@, Stefania Nicola ^*, Antonio Riva ^*, Mara Biasin , Mario Clerici , and Maria Luisa Villa ^*

Dipartimentos di *Scienze e Tecnologie Biomediche and Scienze Precliniche, Cattedra di Immunologia, Università degli Studi di Milano, Italy

^@ To whom correspondence should be addressed. E-mail: silvia.dellabella{at}unimi.it.

	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- (IFN-DCs). We found that IFN- 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-, 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-) 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.

Key Words: antigen presenting cells • cytokines • Th1/Th2

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