The Cytokine Profile Expressed by Human Dendritic Cells Is Dependent on Cell Subtype and Mode of Activation

• Published in: The Journal of immunology (1950) 1998-02, Vol.160 (4), p.1666-1676
• Main Authors: de Saint-Vis, Blandine, Fugier-Vivier, Isabelle, Massacrier, Catherine, Gaillard, Claude, Vanbervliet, Beatrice, Ait-Yahia, Smina, Banchereau, Jacques, Liu, Yong-Jun, Lebecque, Serge, Caux, Christophe
• Format: Article
• Language: English
• Subjects: Antigens, CD1 - analysis; Antigens, CD34 - analysis; Cells, Cultured; Child; Cytokines - biosynthesis; Cytokines - genetics; Dendritic Cells - classification; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - secretion; Fetal Blood - cytology; Fetal Blood - immunology; Hematopoietic Stem Cells - immunology; Humans; Interleukin-10 - biosynthesis; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Interleukin-12 - secretion; Interleukin-13 - biosynthesis; Interleukin-18; Interleukin-7 - biosynthesis; Interleukin-7 - genetics; Ionomycin - pharmacology; Langerhans Cells - immunology; Langerhans Cells - metabolism; Langerhans Cells - secretion; Lipopolysaccharide Receptors - analysis; Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Signal Transduction - drug effects; Signal Transduction - immunology; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.4.1666

In the present study, we have analyzed the pattern of cytokines expressed by two independent dendritic cell (DC) subpopulations generated in vitro from human cord blood CD34+ progenitors cultured with granulocyte-macrophage CSF and TNF-alpha. Molecularly, we confirmed the phenotypic differences discriminating the two subsets: E-cadherin mRNA was only detected in CD1a+-derived DC, whereas CD68 and factor XIIIa mRNAs were observed exclusively in CD14+-derived DC. Semiquantitative reverse-transcriptase PCR analysis revealed that both DC subpopulations spontaneously expressed IL-1alpha, IL-1beta, IL-6, IL-7, IL-12 (p35 and p40), IL-15, IL-18, TNF-alpha, TGF-beta, macrophage CSF, and granulocyte-macrophage CSF, but not IL-2, IL-3, IL-4, IL-5, IL-9, and IFN-gamma transcripts. Both subpopulations were shown to secrete IL-12 after CD40 triggering. Interestingly, only the CD14+-derived DC secreted IL-10 after CD40 activation, strengthening the notion that the two DC subpopulations indeed represent two independent pathways of DC development. Furthermore, both DC subpopulations expressed IL-13 mRNA and protein following activation with PMA-ionomycin, but not with CD40 ligand, in contrast to IL-12 and IL-10, revealing the existence of different pathways for DC activation. Finally, we confirmed the expression of IL-7, IL-10, and IL-13 mRNA by CD4+ CD11c+ CD3- DC isolated ex vivo from tonsillar germinal centers. Thus, CD14+-derived DC expressing IL-10 and factor XIIIa seemed more closely related to germinal center dendritic cellsGCDC than to Langerhans cells.