FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.

Journal Article

BACKGROUND: FK506-binding proteins (FKBP) are immunophilins that interact with the immunosuppressive drugs FK506 and rapamycin. Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells. It has been speculated that these FKBPs are possibly redundant in the immunosuppressant-induced T-cell inactivation. To determine the pharmacological relevance of multiple FKBP members in the immunosuppressant-induced T-cell inactivation, we have investigated the physiological responses of FKBP12-deficient and FKBP12.6-deficient mutant T cells to the immunosuppressive agent FK506. METHODS: FKBP12-deficient and FKBP12.6-deficient T cells were isolated from genetically engineered FKBP12-deficient and FKBP12.6-deficient mice, respectively. T-cell growth inhibitory assay was used to assess their responses to immunosuppressant FK506 treatments. RESULTS: We found that growth inhibition induced by FK506 is abolished in FKBP12-deficient cells but not in FKBP12.6-deficient cells. CONCLUSIONS: FKBP12 is the only FKBP family member that plays a key role in immunosuppressant-mediated immunosuppression.

Full Text

Duke Authors

Cited Authors

  • Xu, X; Su, B; Barndt, RJ; Chen, H; Xin, H; Yan, G; Chen, L; Cheng, D; Heitman, J; Zhuang, Y; Fleischer, S; Shou, W

Published Date

  • June 15, 2002

Published In

Volume / Issue

  • 73 / 11

Start / End Page

  • 1835 - 1838

PubMed ID

  • 12085010

International Standard Serial Number (ISSN)

  • 0041-1337

Language

  • eng

Conference Location

  • United States