IFN-beta interferes with the differentiation of dendritic cells from peripheral blood mononuclear cells: selective inhibition of CD40-dependent interleukin-12 secretion.
We studied the effects of interferon-beta (IFN-beta) on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells (PBMC) from a total of 30 healthy volunteers in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). First, we found that the addition of IFN-beta at the initiation of the culture did not modify DC morphology but caused a reproducible and statistically significant upregulation of HLA-DR, CD86, and CD80 surface expression. CD1a expression was significantly reduced, and CD40 expression was unchanged. We then determined the influence of IFN-beta on the production of cytokines by DC. DC differentiated in the presence of IFN-beta secreted significantly less IL-12 (p40 and p70) both spontaneously and on activation by fibroblasts transfected with the CD40L gene. This effect of IFN-beta was dose dependent and selective, as it was not observed for IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha). As a consequence, DC differentiated in the presence of IFN-beta induced significantly less IFN-gamma secretion by alloreactive T cells, whereas they were more efficient than control DC in eliciting IL-5 secretion. We conclude that the direct action of IFN-beta on DC causes inhibition of their ability to secrete IL-12 in response to CD40 ligation and to elicit Th1 type responses.
Bartholomé
E J
EJ
Department of Immunology, Hôpital Erasme, Brussels, Belgium.
Willems
F
F
Crusiaux
A
A
Thielemans
K
K
Schandene
L
L
Goldman
M
M
D019013:CD40 Antigens / Q000097:blood*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D015203:Reproducibility of Results; D012636:Secretory Rate / Q000187:drug effects
D019013:CD40 Antigens; D011994:Recombinant Proteins; D018664:Interleukin-12; D016899:Interferon-beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor