Is it wise to target the late costimulatory molecule OX40 as a therapeutic target?

REVIEW

DOI: 10.1007/s00005-008-0032-3

Cite this article as:
Cavanagh, M.M. & Hussell, T. Arch. Immunol. Ther. Exp. (2008) 56: 291. doi:10.1007/s00005-008-0032-3

Abstract

The immune response triggered following pathogen recognition, though required to clear the infection, can be detrimental if it is produced in excess or fails to resolve promptly. Excessive inflammation contributes to infectious and noninfectious pathologies in the gut (such as inflammatory bowel disease), lung (such as bronchiolitis), and in a variety of autoimmune conditions. T cells contribute significantly to pathology during inflammation. Global anti-inflammatory strategies can alleviate the consequences of exuberant inflammation by suppressing T cell activity, but may leave the patient vulnerable to opportunistic infection. More specific therapies aim to suppress only those T cells involved in the disease process, and one such approach is to target late costimulatory molecules. These are not expressed on naïve or resting memory cells. Rather, they have a specific window of expression and their ligation results in the production of abundant inflammatory cytokines. By targeting these molecules, it is hoped that inflammation will reduce, but that therapies will be specific enough to avoid, global immune suppression. This review focuses on the late costimulatory molecule OX40, compare it with other T cell costimulators, and highlight why it is a more suitable target for immune intervention than other immune suppressive strategies.

Keywords:

costimulatory molecules autoimmunity infection OX40 immunopathology 

Abbreviations:

APC

antigen-presenting cell

IL

interleukin

ICOS

inducible costimulator

MHC

major histocompatibility complex

OX40L

OX40 ligand

TCR

T cell receptor

TNF

tumor necrosis factor

TNFRSF

TNF receptor superfamily

TNFSF

TNF superfamily

TRAF

TNF receptor-associated factor

Treg

regulatory T cells

Copyright information

© Birkhaueser 2008

Authors and Affiliations

  1. 1.Imperial College LondonNational Heart and Lung InstituteLondonUK

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