Roles of OX40 in the pathogenesis and the control of diseases.
OX40 belongs to the tumor necrosis factor receptor superfamily, and its expression is restricted to activated T-cells. Ligation of OX40 during T-cell-dendritic cell interaction is crucial for clonal expansion of antigen-specific T-cells and generation of T-cell memory. The ligand of OX40 (OX40L) is expressed not only on dendritic cells but also on other cell types, such as B-cells, vascular endothelial cells, natural killer cells, and mast cells. The pathophysiological relevance of this broad distribution needs further investigation. In particular, OX40L on vascular endothelial cells may play a role in inflammatory vasculitis as well as in atherosclerotic change. Recent studies with animal models have indicated the critical involvement of OX40 in the pathogenesis of a variety of immunologic abnormalities of inflammatory, autoimmune, infectious, allergic, and allotransplantation-related diseases. Blockade of OX40-OX40L interaction has been shown to prevent, cure, or ameliorate these diseases. In contrast, activation of OX40 is known to break an existing state of tolerance in malignancies, leading to a reactivation of antitumor immunity. These findings clearly suggest that the OX40/OX40L system is one of the most promising targets of immune intervention for treatment of these diseases.
Hori
Toshiyuki
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. thori@kuhp.kyoto-u.ac.jp
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000276:immunology*; D007239:Infections / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D053278:OX40 Ligand; D009928:Organ Specificity / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014181:Transplantation Immunology / Q000276:immunology*; D048069:Tumor Necrosis Factors / Q000276:immunology
D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; D048069:Tumor Necrosis Factors