Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin.

Journal Article (Journal Article;Review)

The immunosuppressant cyclosporine A revolutionized treatment of graft rejection. Two newer agents, FK506 and rapamycin, show great clinical potential. These drugs suppress the immune system by forming protein-drug complexes that interact with and inhibit key components of the signal transduction pathways required for T-cell activation. The target of the cyclophilin A-cyclosporine A and FKBP12-FK506 complexes is calcineurin, a protein phosphatase required for signaling via the T-cell receptor. Cyclosporine A and FK506 nephrotoxicity may reflect renal-specific functions of calcineurin. The target of the FKBP12-rapamycin complex is TOR, a lipid and protein kinase homolog that is likely to be required for T-cell proliferation in response to interleukin-2. The identification of cyclosporine A, FK506, and rapamycin targets reveals much concerning T-cell signaling and provides the means to design novel immunosuppressants with reduced toxicity.

Full Text

Duke Authors

Cited Authors

  • Cardenas, ME; Zhu, D; Heitman, J

Published Date

  • November 1995

Published In

Volume / Issue

  • 4 / 6

Start / End Page

  • 472 - 477

PubMed ID

  • 8591053

International Standard Serial Number (ISSN)

  • 1062-4821

Digital Object Identifier (DOI)

  • 10.1097/00041552-199511000-00002


  • eng

Conference Location

  • England