Best Practice & Research Clinical Rheumatology
Volume 24, Issue 4 , Pages 463-477, August 2010

Co-stimulation and T cells as therapeutic targets

  • Alison M. Gizinski

      Affiliations

    • Division of Rheumatology, Department of Internal Medicine and Rheumatic Disease Core Center, University of Michigan, 1500 East Medical Center Drive, 3918Taubman Center, SPC 5358, Ann Arbor, Michigan 48109, USA
    • Tel.: +1 734 936 5560; Fax: +1 734 763 1253.
    • ,
  • David A. Fox

      Affiliations

    • Division of Rheumatology, Department of Internal Medicine and Rheumatic Disease Core Center, University of Michigan, 1500 East Medical Center Drive, 3918Taubman Center, SPC 5358, Ann Arbor, Michigan 48109, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 734 936 5560; Fax: +1 734 763 1253.
    web address
    • ,
  • Sujata Sarkar

      Affiliations

    • Section of Rheumatology, Department of Medicine, University of Arizona, 1501 North Campbell Avenue, Rm 6310, Tucson, Arizona 85724, USA
    • Tel.: +1 520 626 5727; Fax: +1 520 626 9366.

Full activation and differentiation of resting T cells into effector T cells requires at least two signals, the first through engagement of the T cell antigen receptor (TCR) by the antigen-major histocompatibility complex (MHC) on antigen-presenting cells (APCs), and the second by engagement of co-stimulatory molecules such as CD28, on T cells by ligands such as CD80/86 on APCs. Effector T cell differentiation is associated with proliferation, secretion of cytokines and expression of additional surface molecules. These inducible structures may have stimulatory (ICOS, OX40 and 4-1BB) or inhibitory (cytotoxic T-lymphocyte antigen (CTLA)-4) potential. To the extent that T cells have a role in particular immune-mediated diseases, interruption of T cell co-stimulation is a potentially worthwhile approach to the treatment of those conditions. This article summarises the experience in treating rheumatological disease by perturbation of T cell co-stimulation, and also describes structures that could be future targets for this type of therapeutic approach.

Keywords: T lymphocytes, rheumatoid arthritis, CD antigens

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PII: S1521-6942(09)00160-0

doi:10.1016/j.berh.2009.12.015

Best Practice & Research Clinical Rheumatology
Volume 24, Issue 4 , Pages 463-477, August 2010

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