Dissecting the mechanism of T-cell anergy with immunophilin ligands.

T-cell receptor engagement in the absence of costimulation leads to T-cell anergy. The biochemical and molecular mechanisms responsible for this form of T-cell tolerance are becoming better defined. This review examines the intersection between T-cell receptor-induced anergy and the immunophilin ligands ciclosporin A, FK-506, rapamycin and sanglifehrin A, and focuses on how these compounds play an important role in dissecting the pathways leading to the induction and maintenance of anergy. Finally, the clinical role of these compounds as immunosuppressive agents will be discussed in the context of their effects on promoting or inhibiting T-cell anergy.