title: FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.
abstract: 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.
authors.affiliation: Herman B. Wells Center for Pediatric Research, Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Barndt
authors.forename: Hanying
authors.initials: H
authors.lastname: Chen
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xin
authors.forename: Guifan
authors.initials: G
authors.lastname: Yan
authors.forename: Linyuan
authors.initials: L
authors.lastname: Chen
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cheng
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Sidney
authors.initials: S
authors.lastname: Fleischer
authors.forename: Weinian
authors.initials: W
authors.lastname: Shou
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology*; D022061:Tacrolimus Binding Protein 1A / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D022061:Tacrolimus Binding Protein 1A; D016559:Tacrolimus