T-cell costimulation blockade in immunologic diseases: role of CD28 family members.
The destruction of many immune-mediated diseases is a result of T-cell responses against usually harmless antigens. Extensive research has been conducted to discover new mechanisms to specifically modulate harmful effector T cells while leaving normal immune responses intact. Since proteins of the CD28 family members are expressed on T cells, blockade of these proteins has become a possible target for potential therapies. The CD28 family contains proteins that have the ability to both enhance and diminish T-cell responses. Therefore, blockade of targets that enhance T-cell signaling may reduce destructive autoimmune responses, while blockade of targets that diminish T-cell signaling may enhance antitumor responses. In this article, the function of these proteins will be reviewed and a sample of clinical trials highlighting the potential efficacy and drawbacks of their use in humans will be described briefly. Finally, inducible costimulator and programmed death-1, two future targets of T-cell therapies, will be highlighted.
Clay
Bryan S
BS
University of Chicago, The Committee on Immunology, Department of Medicine, MC 6076, 5841 S. Maryland Ave, Chicago, IL 60637, USA. bclay@uchicago.edu
Sperling
Anne I
AI