4-1BB Ligand Stimulation Enhances Myeloid Dendritic Cell Maturation from Human Umbilical Cord Blood CD34 + Progenitor Cells

Abstract

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.