Organ transplantation: modulation of T-cell activation pathways initiated by cell surface receptors to suppress graft rejection.

T-cell activation depends upon two types of signals: a T-cell-receptor-mediated antigen-specific signal and several non-antigen-specific ones provided by the engagement of costimulatory and/or inhibitory T-cell surface molecules. In clinical transplantation, T-cell costimulatory/inhibitory molecules are involved in determining cytokine production, vascular endothelial cell damage, and induction of transplant rejection. Several of the latest new immunotherapeutic strategies being currently developed to control graft rejection aim at inhibiting alloreactive T-cell function by regulating activating and costimulatory/inhibitory signals to T cells. This article describes the recent development and potential application of these therapies in experimental and pre-clinical transplantation.