EXPRESSION AND FUNCTION OF OX40 LIGAND ON HUMAN DENDRITIC CELLS

OX40 ligand (OX40L), a member of the TNF family, was shown to be capab le of signaling both the cells on which it is expressed and those expr essing OX40, its cognate receptor. Here we show that OX40L is expresse d on dendritic cells (DC), the mast efficient APC to prime naive T cel ls. The expression and the functional activity of OX40L were examined by means of mAbs used to stain or cross-link OX40L on 1) freshly isola ted human blood DC (bDC) and 2) monocyte-derived DC at different stage s of differentiation. These were derived from monocytes cultured eithe r with IL-4 and granulocyte-macrophage CSF (IL-4-Mo-DC) or with IL-4 a nd granulocyte-macrophage CSF plus TNF-alpha. Both types of Mo-DC expr essed OX40L after stimulation through CD40; ligation of OX40L on activ ated IL-4-Mo-DC enhanced by 4- to 35-fold their cytokine production (T NF-alpha, IL-12 p40, IL-1 beta, and IL-6) and increased CD80, CD86, CD 54, and CD40 expression. Stimulation of activated IL-4-Mo-DC through O X40L strikingly enhanced their maturation as evidenced by CD83 up-regu lation, CD115 (CSF-1R) down-regulation, and typical morphologic change s. OX40L was constitutively expressed on a subset of bDC, and its liga tion slightly enhanced CD40L-stimulated IL-12 production. OX40L was do wn-regulated after overnight culture and spontaneously reexpressed on a subset of mature bDC (CD83(high), CD33(high), CD11c(high), CD5(+)). Thus, the expression of OX40L on DC suggests a physiologic role of thi s molecule during T cell priming by virtue of its ability to costimula te both T cell and DC activation and differentiation.