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Nat Med. 2001 Aug;7(8):907-12.

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

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Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, California, USA.


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.

[Indexed for MEDLINE]

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