CD28 B7 SYSTEM OF T-CELL COSTIMULATION

T cells play a central role in the initiation and regulation of the im mune response to antigen. Both the engagement of the TCR with MHC/Ag a nd a second signal are needed for the complete activation of the T cel l. The CD28/B7 receptor/ligand system is one of the dominant costimula tory pathways. Interruption of this signaling pathway with CD28 antago nists not only results in the suppression of the immune response, but in some cases induces antigen-specific tolerance. However, the CD28/B7 system is increasingly complex due to the identification of multiple receptors and ligands with positive and negative signaling activities. This review summarizes the state of CD28/B7 immunobiology both in vit ro and in vivo; summarizes the many experiments that have led to our c urrent understanding of the participants in this complex receptor/liga nd system; and illustrates the current models for CD28/B7-mediated T c ell and B cell regulation. It is our hope and expectation that this re view will provoke additional research that will unravel this important , yet complex, signaling pathway.