Maturation of dendritic cells by recombinant human CD40L-trimer leads to ahomogeneous cell population with enhanced surface marker expression and increased cytokine production
Pa. Wurtzen et al., Maturation of dendritic cells by recombinant human CD40L-trimer leads to ahomogeneous cell population with enhanced surface marker expression and increased cytokine production, SC J IMMUN, 53(6), 2001, pp. 579-587
Dendritic cells (DC) have been shown to be potent inducers of specific cyto
toxic T-cell responses both in vivo and in vitro. Furthermore, exposure to
cytokines such as tumour necrosis factor (TNF)-alpha or CD40 triggering cha
nges DC phenotype and cytokine production and may enhance the T-cell activa
ting capacity of the DC. We studied DC phenotype and cytokine production as
well as the T-cell proliferation and cytotoxic T lympocyte (CTL) activatio
n induced by DC generated in vitro. In addition, the effect of exposure to
recombinant human CD40L-trimer (huCD40LT) on these parameters was investiga
ted. Effective differentiation of monocytes derived from freshly isolated p
eripheral blood mononuclear cells (PBMC) was obtained with granulocyte macr
ophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. The DC ex
pression of human leucocyte antigen (HLA) molecules, CD80, CD83, and CD86 w
as markedly enhanced by exposure to huCD40LT even compared to TNF-alpha exp
osure. Only a moderate cytokine production was observed initially, while TN
F-alpha addition or CD40 triggering, especially, induced enhanced productio
n of IL-6 and IL-12 p40. Surprisingly, comparable induction of T-cell proli
feration by a DC allostimulus or through the presentation of PPD, and influ
enza M1-peptide specific CTL activity was obtained with nonmaturated (CD83(
-)) and maturated (CD83(+)) DC. In conclusion, a final maturation of monocy
te-derived DC through huCD40LT resulted in a highly homogeneous cell popula
tion with enhanced surface marker expression and high production of pro-inf
lammatory cytokines. In addition, the induction of responses to allo or rec
all antigens presented by huCD40LT maturated DC was comparable to the respo
nses obtained with the DC maturated through TNF-alpha exposure.