Blockade of costimulatory pathways of T-cell activation: the solution to acute and chronic rejection?

Understanding of how antigen-specific signals and costimulatory molecules are involved in T-cell activation has resulted in new strategies to interfere with allograft rejection. The present review focuses on the role of two receptor-ligand pairs: CD28 and cytotoxic T lymphocyte associated antigen-4, which interact with the B7 ligands (CD80, CD86); and CD40, which interacts with the CD40L (CD154). On the basis of the extensive tissue distribution of CD40, it is likely that the CD40/CD40L system plays a much broader role.