New Look at Therapeutic Strategies for Blocking Costimulatory Signal in Experimental and Pre-Clinical Transplantation

The activation of T cells depends upon two signals, antigen-specific signal through the T cell receptor and nonantigen- specific costimulatory signal through antigen present cell surface molecules. In clinical transplantation, activated T cells orchestrate the immune response and result in allograft acute rejection. Allograft chronic rejection is also a serious complication and a major cause of late allograft loss after the transplantation. Costimulatory molecules involve in determining T cell activation, cytokine production, vascular endothelial cell damage, and induction of transplant tolerance. An emerging therapeutic strategy provides methods for inhibiting undesired T-cell activation, proliferation and function by blocking costimulatory interactions. This review article describes the roles of costimulation pathways in the progression of acute and chronic allograft rejection, particularly focuses on the recent development and application of costimulatory blockers in experimental and pre-clinical transplantation.