FK506 and rapamycin: novel pharmacological probes of the immune response.

The immune system is an intricate network of circuitry which is incompletely understood. Novel tools are needed to unravel the relevance of even the smallest components of this network. While the clinical potential of FK506 and rapamycin as selective immunosuppressants is the major reason for their current importance, preclinical studies described here by Joseph Chang and colleagues have already suggested several provocative ideas which may revise our biochemical concepts of T-cell activation. With the combination of molecular and cellular studies, the insights gained with FK506/rapamycin may lead to a better understanding of the biochemical circuits that are involved in the immune response. Ultimately, studies may lead to the identification of an endogenous immunosuppressive ligand that mimics FK506 or rapamycin.