Transcript profiling of human dendritic cells maturation-induced under defined culture conditions: comparison of the effects of tumour necrosis factor alpha, soluble CD40 ligand trimer and interferon gamma.
Using cDNA arrays, we characterized patterns of gene expression in populations of human dendritic cells (DCs) produced for clinical use. Culture and maturation induction of myeloid adherent cells under serum-free conditions yielded DCs with phenotypes similar to those described in serum-based systems. Analysis of gene expression in DCs treated with tumour necrosis factor alpha, soluble CD40L trimer or interferon gamma, however, showed specific patterns for each factor examined. Our studies document the expression of several transcripts that have not hitherto been described in DCs and/or differentially regulated according to the differentiation state of the DCs, and suggest important functional differences among the DC populations examined. In addition, DC maturation directs changes in the levels of mRNA specific for transcriptional regulators that effect the production of cytokines (e.g. BCL-6, c-rel). Other changes observed, including alteration in the gene expression profile of adhesion molecules and chemokine receptors such as CD44H, CD 49B, Rantes R, CXCR5 and CD37, suggest differences in trafficking potential between the populations studied. This broad-based description of DC populations, produced under serum-free conditions, has enabled us to better define intermediate stages of DC maturation as well as the differentiation-inducing effects of cytokines on these cells.
Moschella
F
F
Department of Medicine, Division of Oncology and the DiBella Immunotherapy Research Laboratory, College of Physicians and Surgeons of Columbia University, USA.
Maffei
A
A
Catanzaro
R P
RP
Papadopoulos
K P
KP
Skerrett
D
D
Hesdorffer
C S
CS
Harris
P E
PE
D001483:Base Sequence; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D018076:DNA, Complementary / Q000032:analysis; D003713:Dendritic Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4; D015851:Interleukin-7 / Q000494:pharmacology; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D018076:DNA, Complementary; D015851:Interleukin-7; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor