Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

Even though T-cell-directed trials have been of limited success, is there reason for optimism?

Nature Clinical Practice Rheumatology volume 2, pages 58–59 (2006)Cite this article

It has been proposed that rheumatoid arthritis (RA) is a disease of dysregulated T-cell function.1 This is an important hypothesis, as animal models of allotransplantation and human autoimmune diseases have shown that by manipulating T-cell activation mechanisms, not only can a prolonged therapeutic benefit be induced, but also a permanent state of unresponsiveness, known as tolerance. T-cell tolerance can be induced by a variety of mechanisms including deletion of disease-causing T-cell clones, anergy or failure of response of such T cells, deviation of disease-causing type 1 T-HELPER LYMPHOCYTES (TH1) to nonpathogenic cells (TH2), and the induction of regulatory cells that inhibit the action of disease-causing T cells. A number of experimental approaches have been used to investigate and exploit these mechanisms for therapeutic effects in both human and animal model systems. The application of this knowledge to human disease is still in its infancy. The task at hand is undoubtedly complex, difficult and potentially hazardous because of the pivotal role of T cells in adaptive immune responses, without which our existence as free-living organisms would be compromised. The prize, however, is so valuable that researchers must persevere in this endeavor.

The success of anti-tumor-necrosis-factor biologic therapies has put the need for and, indeed, the relevance of, developing anti-T-cell therapies in doubt. Improvements have been observed in some patients receiving these therapies; however, these improvements are only maintained whilst treatment is administered and cessation of therapy leads to flare of the disease. This response has been predicted since it was known that the underlying mechanism that drives rheumatoid inflammation, the T cell, is still active.2 This effect will also apply to other therapies that are directed at distal events in the inflammatory cascade, such as inhibition of interleukin-6, interleukin-1 and others. The fact that such expensive therapies will have to be continued, possibly for the lifetime of the patient, will impose a considerable financial burden on health systems and perhaps lead to the development of serious adverse events. The rational choice, therefore, is to manipulate the T-cell response by inducing an unresponsive state so that treatment is either infrequent or given as a single course at the beginning of therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Janossy G et al. (1981) Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. Lancet 17: 839–842

    Article  Google Scholar 

  2. Panayi GS (1995) The pathogenesis of rheumatoid arthritis and the development of therapeutic strategies for the clinical investigation of biologics. Agents Actions Suppl 47: 1–21

    CAS  PubMed  Google Scholar 

  3. Choy EHS et al. Immunotherapies: T cell, B cell and complement. In Rheumatology, edn 3, 449–454 (Eds Hochberg MC et al.) Philadelphia: Mosby

  4. Choy EH et al. (2002) Repeat-cycle study of high-dose intravenous 4162W94 anti-CD4 humanized monoclonal antibody in rheumatoid arthritis. A randomized placebo-controlled trial. Rheumatology 41: 1142–1148

    Article  CAS  Google Scholar 

  5. Mason U et al. (2002) CD4 coating, but not CD4 depletion, is a predictor of efficacy with primatized monoclonal anti-CD4 treatment of active rheumatoid arthritis. J Rheumatol 29: 220–229

    CAS  PubMed  Google Scholar 

  6. Moreland LW et al. (1998) T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vβ3, Vβ14, and Vβ17 peptides. Arthritis Rheum 41: 1919–1929

    Article  CAS  Google Scholar 

  7. Choy EH et al. (2001) Control of rheumatoid arthritis by oral tolerance. Arthritis Rheum 44: 1993–1997

    Article  CAS  Google Scholar 

  8. Prakken BJ et al. (2004) Epitope-specific immunotherapy induces deviation of pro-inflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci 101: 4228–4233

    Article  CAS  Google Scholar 

  9. Kremer JM et al. (2003) Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med 349: 1907–1915

    Article  CAS  Google Scholar 

  10. Panayi GS (2005) B cell-directed therapy in rheumatoid arthritis—clinical experience. J Rheumatol Suppl 73: 19–24

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Arthritis Research Campaign Professor of Rheumatology at the Department of Rheumatology, Guy's Hospital, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK

    Gabriel S Panayi

Authors
  1. Gabriel S Panayi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriel S Panayi.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Panayi, G. Even though T-cell-directed trials have been of limited success, is there reason for optimism?. Nat Rev Rheumatol 2, 58–59 (2006). https://doi.org/10.1038/ncprheum0094

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0094

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing