CD137 ligand signaling induces human monocyte to dendritic cell differentiation.

The ligand for CD137 (4-1BB) is expressed on peripheral human monocytes and delivers a potent activating signal via reverse signaling. Here we show that treatment of monocytes with a recombinant CD137 protein that induces reverse signaling through CD137 ligand reduces typical macrophage characteristics such as phagocytosis, oxidative burst and CD14 expression; however, typical DC characteristics including endocytosis, costimulatory molecule expression and the ability to stimulate proliferation of naïve T cells are induced. CD137-generated DC do not express DC-SIGN, CD1a or IL-12 and secrete less IL-10 than classical DC. CD137-generated DC are mature, and addition of LPS+IFN-gamma does not enhance their T-cell-stimulatory capacity. This indicates that CD137 as a sole factor is sufficient to induce development to mature DC, making stimulation of CD137 ligand the most simple protocol to generate mature DC. CD137-generated DC are more potent in inducing T-cell proliferation than classical DC. They inhibit development of Treg cells but induce T-cell expression of perforin, IFN-gamma, IL-13 and IL-17. These data demonstrate that CD137 as a single factor is sufficient to induce differentiation of peripheral monocytes to mature inflammatory DC that have a more potent T-cell-stimulatory capacity than classical DC.