Premium
IL‐4 and CD40 ligation affect differently the differentiation, maturation, and function of human CD34 + cell‐derived CD1a + CD14 – and CD1a – CD14 + dendritic cell precursors in vitro
Author(s) -
Canque Bruno,
Camus Sandrine,
Yagello Micael,
Gluckman Jean Claude
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.2.235
Subject(s) - biology , cd14 , dendritic cell , microbiology and biotechnology , function (biology) , in vitro , cellular differentiation , cd40 , immunology , immune system , biochemistry , gene , cytotoxic t cell
We examined the effect of interleukin (IL)‐4 or CD40 ligation on the differentiation and maturation of CD1a + CD14 – and CD1a – CD14 + dendritic cell (DC) precursors. Cord blood CD34 + cells were cultured with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and tumor necrosis factor α (TNF‐α), to which stem cell factor and Flt‐3 ligand were added for 5 days. Phenotypic analysis of DC precursors on culture day 7 showed that CD1a + CD14 – cells expressed higher CD11c and CD80 levels and lower CD116/GM‐CSFR and CCR‐5 levels than their CD1a – CD14 + counterparts. Culturing CD1a + CD14 – precursors with GM‐CSF and TNF‐α resulted in DC with heterogeneous CD1a, HLA;SMDR (DR), CD11b, and CD83 expression, 10% of which acquired CD14. IL‐4 and CD40 ligation affected their differentiation in contrasting ways: IL‐4 induced CD1a hi CD14 – DR lo CD11b + CD83 – S100 + DC with reduced MLR‐stimulating capacity, whereas CD40 ligation led to CD1a lo/‐ CD14 – CD40 – DR hi CD11b – CD83 + S100 +/– DC with stronger MLR‐stimulating capacity. Also, both IL‐4 and CD40 ligation promoted RelB expression and nuclear translocation. When CD1a – CD14 + precursors were maintained in only the presence of GM‐CSF and TNF‐α, this led to mixed populations of adherent macrophages and nonadherent CD1a – CD14 + monocytes, and of CD1a + CD14 – and CD1a + CD14 + DC, which were DR lo CD11b + ‐CD83 – S100 – . IL‐4 or CD40 ligation prevented their differentiation into macrophages and resulted in DC with phenotypes close to those issued from CD1a + CD14 – precursors, with only a minority staying CD14 + but most being S100 – ; their MLR‐stimulating capacity also increased but remained lower than that of DC differentiated from CD1a + CD14 – precursors. Thus, IL‐4 or CD40 ligation induced CD1a + CD14 – and CD1a – CD14 + DC precursors to differentiate into phenotypically close but functionally different DC populations, suggesting that DC function is primarily determined by their origin. The heterogeneity of DC should then be related to different developmental pathways and to different stages of maturation/activation. J. Leukoc. Biol . 64: 235–244; 1998.