title: IL-4 addition during differentiation of CD34 progenitors delays maturation of dendritic cells while promoting their survival.
abstract: Dendritic cells (DC) are the most effective cells for antigen presentation in primary immune responses. Human cord blood CD34+ progenitors cultured in the presence of GM-CSF and TNF alpha generate a heterogeneous population of DC including Langerhans-like DC (LLDC) and monocytes. We describe here that IL-4 exerts different effecs in such culture according to the cells considered. Thus, IL-4 favors DC components at the expense of monocytic development, and permits long-time persistence of DC which can be maintained up to one month in culture. These results show an IL-4-dependent inhibition of proliferation and emergence of CD14+ cells. Notably, however, IL-4 also acts on the DC precursors. Thus, IL-4 enhances survival and delays maturation of LLDC from CD1a+ CD14- precursors. In addition, IL-4 also favors orientation of CD14+ CD1a- DC/monocyte precursors towards dermal-type CD1a+ DC. DC recovered from IL-4 treated cultures display reduced allostimulatory capacity, but this function is restored upon IL-4 weaning. Finally, a short (48h) IL-4 pulse is sufficient to favor DC development. The present study demonstrates that IL-4 positively regulates DC development at several levels on distinct precursor cells.
authors.affiliation: INSERM Unité 346, Laboratoire de Recherche Peau Humaine et Immunité, Hôpital Edouard Herriot, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Rougier
authors.forename: D
authors.initials: D
authors.lastname: Schmitt
authors.forename: C
authors.initials: C
authors.lastname: Vincent
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D018952:Antigens, CD34; D002454:Cell Differentiation; D002470:Cell Survival; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D005312:Fetal Blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018949:Antigens, CD1; D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor