title: Signaling through OX40 (CD134) breaks peripheral T-cell tolerance.
abstract: Peripheral T-cell tolerance is a mechanism to limit autoimmunity, but represents a major obstacle in diseases such as cancer. Tolerance is due to limited accumulation of antigen-specific T cells accompanied by functional hypo-responsiveness, and is induced by antigen encounter in a non-inflammatory environment. In contrast to advances in preventing induction of T-cell tolerance, there has been little progress in defining targets to reverse established tolerance. Here we show that signals from a single dose of an agonistic antibody against OX40 (CD134, a member of the tumor necrosis-factor family of receptors) can break an existing state of tolerance in the CD4+ T-cell compartment. OX40 signals promote T-cell expansion after the hypo-responsive phenotype is induced and restore normal functionality. These data highlight the potent costimulatory capacity of OX40, and indicate OX40 as a target for therapeutic intervention in a variety of related diseases.
authors.affiliation: Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, California, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bansal-Pakala
authors.forename: A G
authors.initials: AG
authors.lastname: Jember
authors.forename: M
authors.initials: M
authors.lastname: Croft
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology*; D000818:Animals; D051379:Mice; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7