Signaling through OX40 (CD134) breaks peripheral T-cell tolerance

Nat Med. 2001 Aug;7(8):907-12. doi: 10.1038/90942.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological / immunology*
  • Animals
  • Mice
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor*
  • Signal Transduction*
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*


  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7