4-1BB ligand stimulation enhances myeloid dendritic cell maturation from human umbilical cord blood CD34+ progenitor cells

In humans, at least two subsets of dendritic cells (DCs) are identified on the basis of differential surface expression of CD11c antigens. CD11c(+) and CD11c(-) cells are respectively of myeloid and lympholoid origin and functionally distinct, eliciting inflammatory and tolerant T cell responses. We investigated whether 4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) family, is involved in the maturation process to mature myeloid DCs during in vitro DC differentiation from immature DCs-derived from human umbilical cord blood (CB) CD34(+) progenitor cells. Enhanced levels of CD11c as well as immunostimulatory molecules such as CD86, MHC class II, and 4-1BBL were induced in response to 4-1BBL stimulation. These changes were accompanied by noticeable morphological transition from nonadherent to adherent myeloid-like DCs. Stimulation of 4-1BBL on DCs with 4-1BB-Fc or with 4-1BB-transfected Jurkat cells resulted in acquisition of capacity for the immature DCs to produce interleukin-12 (IL-12). This suggests that 4-1BBL may be an important mediator for maturation of CD11c(+) myeloid DCs, information of possible relevance for the design of DC-based vaccines with enhanced activity.