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
Pubmed Central ID
- 12085010
International Standard Serial Number (ISSN)
- 0041-1337
Digital Object Identifier (DOI)
- 10.1097/00007890-200206150-00023
Language
- eng
Conference Location
- United States