CD137 ligand, a member of the tumor necrosis factor family, regulates immune responses via reverse signal transduction

CD137 (4-1BB, TNFR superfamily 9) and its ligand are members of the TNFR and TNF families, respectively, and are involved in the regulation of a wide range of immune activities. CD137 ligand cross-links its receptor, CD137, which is expressed on activated T cells, and costimulates T cell activities. CD137 ligand can also be expressed as a transmembrane protein on the cell surface and transmit signals into the cells on which it is expressed (reverse signaling). CD137 ligand expression is found on most types of leukocytes and on some nonimmune cells. In monocytic cells (monocytes, macrophages, and DCs), CD137 ligand signaling induces activation, migration, survival, and differentiation. The activities of T cells, B cells, hematopoietic progenitor cells, and some malignant cells are also influenced by CD137 ligand, but the physiological significance is understood only partly. As CD137 and CD137 ligand are regarded as valuable targets for immunotherapy, it is pivotal to determine which biological effects are mediated by which of the 2 molecules.