Neonatal dendritic cells are intrinsically biased against Th-1 immune responses.
Dendritic cells (DCs) were derived from human peripheral blood monocytes or cord blood monocytes cultured in the presence of IL-4 and GM-CSF. Adult and cord DCs were observed to have comparable immature phenotypes. However, the increase in surface expression of HLA-DR and CD86 after addition of LPS was significantly attenuated in cord DCs, with CD25 and CD83 expression also markedly reduced. Cord DCs were also unable to produce IL-12p70, failed to down-regulate expression of the chemokine receptor CCR5 and induced lower levels of IFN-gamma production from allogeneic naive CD4+ T cells than their adult counterparts. In contrast, the kinetics of the production of TNF-alpha and IL-10 in response to LPS stimulation was comparable to adult DCs. The reduced ability of cord DCs to attain a fully mature adult phenotype, and to activate naive CD4+ T cells to produce IFN-gamma, suggests that they are intrinsically preprogrammed against the generation of Th-1 immune responses.
Langrish
C L
CL
Molecular Immunology Unit, University College London, UK.
Buddle
J C
JC
Thrasher
A J
AJ
Goldblatt
D
D
D000328:Adult; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007519:Isoantigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10