Augmentation and differentiation of hematopoietic progenitor cells by CD137

Abstract

We identified the expression of CD137 and CD137 ligand on small subsets of bone marrow cells. Activation of hematopoietic progenitor cells through CD137 ligand induces activation, prolongation of survival, proliferation and colony formation. Concomitantly to proliferation, the cells differentiate to CFU-GM, and then to monocytes and macrophages but not to granulocytes or dendritic cells. Hematopoietic progenitor cells differentiated in the presence of CD137 display enhanced phagocytic activity, secrete high levels of IL-10 but no IL-12 in response to LPS, and can partially suppress T cell activation and proliferation in an allogeneic mixed lymphocyte reaction. CD137 and G-CSF cooperatively induce survival and proliferation of murine bone marrow cells, while they compete for inducing monocytic and granulocytic differentiation, respectively. The number of CD137+ cells in the bone marrow is positively regulated during infection and inflammation. These data uncover a novel function of CD137 and CD137 ligand by showing their participation in hematopoiesis.