IL-4 addition during differentiation of CD34 progenitors delays maturation of dendritic cells while promoting their survival.
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.
Rougier
N
N
INSERM Unité 346, Laboratoire de Recherche Peau Humaine et Immunité, Hôpital Edouard Herriot, Lyon, France.
Schmitt
D
D
Vincent
C
C
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
D018949:Antigens, CD1; D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor