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Rheumatology Advance Access published online on May 25, 2008
Rheumatology, doi:10.1093/rheumatology/ken163
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Review

Therapeutic T-cell manipulation in rheumatoid arthritis: past, present and future

J. D. Isaacs

Musculoskeletal Research Group and Wilson Horne Immunotherapy Centre, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.

Correspondence to: J. D. Isaacs, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, 4th Floor Catherine Cookson Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, UK. E-mail: j.d.isaacs{at}ncl.ac.uk


  Abstract

Accumulating evidence suggests that RA is a T-cell-mediated autoimmune disease. Early attempts at disease modulation using strategies such as CD4 mAbs were severely hampered by a lack of biomarkers of autoreactivity. Recently, however, co-stimulation blockade has emerged as an effective treatment for RA. Alongside a greatly improved mechanistic understanding of immune regulation, this has rekindled hopes for authentic and robust immune programming. The final pieces of the jigsaw are not yet in place for RA but, in other disciplines, emerging treatment paradigms such as non-mitogenic anti-CD3 mAbs, autoantigenic peptides and even cellular therapies are providing hope for a future in which immunopathology can be specifically and vigorously curtailed.

KEY WORDS: Rheumatoid arthritis, T cell, Therapeutic tolerance, Anti-CD3, Immune modulation, Monoclonal antibody, Immunotherapy, Co-stimulation blockade, Autoimmunity, Regulatory T cell

Submitted 10 February 2008; revised version accepted 31 March 2008.
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