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Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases

Monika C Brunner-Weinzierl12*, Holger Hoff12 and Gerd-R Burmester2

Author Affiliations

1 Molecular Immunology, Deutsches Rheuma-Forschungszentrum Berlin, Germany

2 Charité, Universitätsmedizin Berlin, Germany

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Arthritis Res Ther 2004, 6:45-54  doi:10.1186/ar1158

Published: 3 March 2004


Chronic T cell responses, as they occur in rheumatoid arthritis, are complex and are likely to involve many mechanisms. There is a growing body of evidence that, in concert with the T cell antigen receptor signal, CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) are the primary regulators of T cell responses. Whereas CD28 primarily activates T cell processes, CTLA-4 inhibits them. The mechanism for this dichotomy is not fully understood, especially as CD28 and CTLA-4 recruit similar signalling molecules. In addition, recent studies demonstrate that CD28 and CTLA-4 have multiple functions during T cell responses. In particular, CTLA-4 exerts independent distinct effects during different phases of T cell responses that could be exploited for the treatment of rheumatoid arthritis.

CD152; costimulation; CTLA-4Ig; inflammation; polymorphism; signal transduction