Roles of OX40 in the pathogenesis and the control of diseases

• Published in: International journal of hematology Vol. 83; no. 1; pp. 17 - 22
• Main Author: HORI, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01.01.2006; Springer Nature B.V
• Subjects: Animals; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Biological and medical sciences; Hematologic and hematopoietic diseases; Humans; Hypersensitivity - immunology; Hypersensitivity - pathology; Immunity, Cellular - immunology; Infection - immunology; Infection - pathology; Medical sciences; Membrane Glycoproteins - immunology; Neoplasms - immunology; Organ Specificity - immunology; OX40 Ligand; Receptors, OX40; Receptors, Tumor Necrosis Factor - immunology; Signal Transduction - immunology; Transplantation Immunology - immunology; Tumor Necrosis Factors - immunology; OX40; Immune intervention; Hematology; T-cell; Pathogenesis; Costimulation; OX40L; Costimulatory receptor OX40
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1532/IJH97.05151

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.