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

Xu X, Su B, Barndt RJ, Chen H, Xin H, Yan G, Chen L, Cheng D, Heitman J, Zhuang Y, Fleischer S, Shou W
Transplantation. 2002 73 (11): 1835-8

PMID: 12085010 · DOI:10.1097/00007890-200206150-00023

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.

MeSH Terms (12)

Animals CD3 Complex CD28 Antigens Cell Division Cyclosporine Dose-Response Relationship, Drug Immunosuppressive Agents Mice Mice, Knockout T-Lymphocytes Tacrolimus Tacrolimus Binding Protein 1A

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