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Cell Death Differ ; 13(2): 250-9, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16110321

ABSTRACT

We have developed a new culture system whereby human hematopoietic progenitors purified from adult peripheral blood extensively proliferate and gradually differentiate into >95% pure monocytic (Mo) cells. At all developmental stages treatment with interleukin (IL)-4+granulocyte-macrophage colony-stimulating factor or IL-4+c-Kit-ligand+FLT-3 ligand switched the Mo precursors into dendritic cells (DCs). The switching capacity decreased only at the end of the culture, when most Mo cells matured to macrophages. Moreover, the Mo precursors were highly susceptible to transduction with lentiviral vectors: once switched to DCs, they maintained the transgene expression, as well as the phenotype and function of the DC lineage. Our results provide new insight into the potential role of the Mo lineage as a reservoir of DCs in vivo. Furthermore, the methodology for transduction of Mo precursors provides a tool to generate genetically modified, normally functioning DCs potentially useful for immunotherapy.


Subject(s)
Cytokines/pharmacology , Dendritic Cells/cytology , Hematopoietic Stem Cells/cytology , Monocytes/cytology , Myelopoiesis/drug effects , Cell Lineage , Cell Proliferation/drug effects , Cells, Cultured , Dendritic Cells/physiology , Gene Expression Regulation , Gene Transfer Techniques , Genetic Vectors , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cells/drug effects , Humans , Immunotherapy , Interleukin-4/pharmacology , Lentivirus/genetics , Membrane Proteins/pharmacology , Monocytes/chemistry , Monocytes/drug effects , Phenotype , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/analysis , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Stem Cell Factor/pharmacology , Transduction, Genetic , Transgenes
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