Deficient IL-12(p35) gene expression by dendritic cells derived from neonatal monocytes.
To gain insight into the defects responsible for impaired Th1 responses in human newborns, we analyzed the production of cytokines by dendritic cells (DC) derived from cord blood monocytes. We observed that neonatal DC generated from adherent cord blood mononuclear cells cultured for 6 days in the presence of IL-4 and GM-CSF show a phenotype similar to adult DC generated from adherent PBMC, although they express lower levels of HLA-DR, CD80, and CD40. Measurement of cytokine levels produced by neonatal DC upon stimulation by LPS, CD40 ligation, or poly(I:C) indicated a selective defect in the synthesis of IL-12. Determination of IL-12(p40) and IL-12(p35) mRNA levels by real-time RT-PCR revealed that IL-12(p35) gene expression is highly repressed in stimulated neonatal DC whereas their IL-12(p40) gene expression is not altered. The addition of rIFN-gamma to LPS-stimulated newborn DC restored their expression of IL-12(p35) and their synthesis of IL-12 (p70) up to adult levels. Moreover, we observed that neonatal DC are less efficient than adult DC to induce IFN-gamma production by allogenic adult CD4(+) T cells. This defect was corrected by the addition of rIL-12. We conclude that neonatal DC are characterized by a severe defect in IL-12(p35) gene expression which is responsible for an impaired ability to elicit IFN-gamma production by T cells.
Goriely
S
S
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Brussels, Belgium.
Vincart
B
B
Stordeur
P
P
Vekemans
J
J
Willems
F
F
Goldman
M
M
De Wit
D
D
D000328:Adult; D000954:Antigens, Surface / Q000096:biosynthesis; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics; D007519:Isoantigens / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D000954:Antigens, Surface; D007519:Isoantigens; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma