CD137 (4-1BB), more than a costimulator

CD137 (4-1BB) is a member of the tumor necrosis factor (TNF) receptor superfamily. It was reported that CD137 expresses on the surface of activated T cells and signaling through CD137 costimulates T cell growth and induces regression of established tumors. We demonstrated that CD137 is expressed at high levels on natural killer (NK) cells and CD137 signaling by an agonistic monoclonal antibody (mAb) promotes the activation of and IFN-γ production from NK cells in the presence of IL-2. These results support a direct role of CD137 signaling in NK cell activation. In addition, freshly isolated mouse splenic dendritic cells (DCs) and bone marrow-derived DCs express CD137 on the cell surface and in soluble form. Triggering CD137 increased the secretion of IL-6 and IL-12 from DCs. More importantly, infusion of an agonistic monoclonal antibody to CD137 into naive mice enhanced the ability of DCs to stimulate T-cell proliferation in response to both alloantigens and a nominal antigen in vitro. This enhancement of DC function is not mediated through activation of T cells since the effect was also observed in RAG-1 knockout mice that lack T cells. Our findings implicate CD137 as an important receptor involved in the modulation of NK and DC function, in addition to costimulatory function for T cells.