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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-4-9
pubmed:abstractText
There is increasing clinical interest in dendritic cells that are capable of initiating antitumor immune responses. Dendritic cells cultured from human blood mononuclear cells using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) are competent for antigen uptake but express relatively low levels of costimulatory molecules and thus correspond to immature resident tissue dendritic cells. In this study we took advantage of the new dendritic cell-specific marker CD83, which is expressed by mature dendritic cells, to delineate the maturation of cultured human blood dendritic cells. Although dendritic cells cultured with GM-CSF and IL-4 contained transcripts for CD83 as determined by reverse transcription PCR, CD83 protein was barely detectable by flow cytometry, confirming that dendritic cells obtained with this system are immature. However, treatment of dendritic cells with tumor necrosis factor-alpha (TNF-alpha) significantly increased the levels of CD83 transcripts and induced CD83 protein expression in dendritic cells. In contrast to the initiation of dendritic cell culture, which was facilitated by high cell density (5 x 10(6) cells/mL), differentiation into CD83+ dendritic cells required a low cell concentration (0.5 x 10(6) cells/mL). At higher cell density (1 x 10(6) cells/mL), CD83 expression was suppressed and was almost completely prevented at 2 x 10(6) cells/mL. Induction of CD83 expression was accompanied by a strong upregulation of the costimulator B7-2 (CD86) on dendritic cells. While untreated CD83(-) dendritic cells efficiently internalized fluoresceinated Dextran, TNF-alpha treated CD83+ dendritic cells excluded these molecules, confirming that maturation of dendritic cells was associated with the silencing of the antigen-capturing machinery. Morphologically, CD83+ dendritic cells presented with pronounced cytoplasmic projections (veils) characteristic of mature dendritic cells. In summary, we show that cell density critically regulates dendritic cell development. Knowledge of the appropriate conditions for dendritic cell generation and maturation will be important in clinical immunotherapy settings.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
232-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
In vitro generation of CD83+ human blood dendritic cells for active tumor immunotherapy.
pubmed:affiliation
Department of Urology, University of Innsbruck, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't