Rank ligand stimulation induces a partial but functional maturation of human monocyte-derived dendritic cells.

ABSTRACT

Mature dendritic cells (DC) are efficient, antigen-presenting cells required for the stimulation of naive T lymphocytes. Many members of the tumour necrosis factor (TNF) receptor family are involved in DC maturation, such as Fas, CD40, OX40L, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) or RANK (receptor activator of NFkappaB), with different, but often overlapping effects. We focused our attention on RANK DC stimulation, since RANK ligand (RL) is expressed on activated T lymphocytes with different kinetic and expression patterns from the other members of TNF family previously cited. After culture with RL-transfected cells, a significant percentage of immature DC generated from monocytes (Mo-DC) acquired a typical, mature DC morphology and phenotype characterised by up-regulation of CD83, DC-LAMP (lysosome-associated membrane glycoprotein), HLA class I, CD86 and CD54. The functional RL-mediated maturation was demonstrated by a decrease in DC macropinocytosis and acquisition of the capacity to stimulate allogenic T-cells. Among the various cytokines tested, we detected only a weak up-regulation of IL-12p40. Our results show that ligation of RANK on DC cell surfaces is not only a survival stimulus, but also induces a partial and specific mature DC phenotype, the physiological significance of which is under investigation.