FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.
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.
Xu
Xuehong
X
Herman B. Wells Center for Pediatric Research, Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Su
Bing
B
Barndt
Robert J
RJ
Chen
Hanying
H
Xin
Hongbo
H
Yan
Guifan
G
Chen
Linyuan
L
Cheng
Dongsheng
D
Heitman
Joseph
J
Zhuang
Yuan
Y
Fleischer
Sidney
S
Shou
Weinian
W
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
D018106:CD28 Antigens; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D022061:Tacrolimus Binding Protein 1A; D016559:Tacrolimus