Tumor antigen pulsed dendritic cells (DCs) can induce anti-tumor immunity. We studied strategies for the reliable generation of such a tumor vaccine by functional maturation of DCs via interaction of CD40 with its ligand (CD40L, CD154). Exposure of immature DCs to CD40L transgenic cells, soluble recombinant human CD40L molecules or lipopolysaccharide induced expression of the co-stimulatory molecules, CD80 and CD86, and supported an allogeneic mixed leukocyte reaction. In contrast, the release of IL-12, an important mediator of anti-tumor immunity, and antigen-specific expansion and IFN gamma secretion of lymphocytes, was strongly triggered only by DCs exposed to CD40L transgenic cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.