Document Detail

FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.
MedLine Citation:
PMID:  12085010     Owner:  NLM     Status:  MEDLINE    
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.
Xuehong Xu; Bing Su; Robert J Barndt; Hanying Chen; Hongbo Xin; Guifan Yan; Linyuan Chen; Dongsheng Cheng; Joseph Heitman; Yuan Zhuang; Sidney Fleischer; Weinian Shou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  73     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-26     Completed Date:  2002-07-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1835-8     Citation Subset:  IM    
Herman B. Wells Center for Pediatric Research, Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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MeSH Terms
Antigens, CD28 / immunology
Antigens, CD3 / immunology
Cell Division / drug effects,  immunology
Cyclosporine / pharmacology
Dose-Response Relationship, Drug
Immunosuppressive Agents / pharmacology*
Mice, Knockout
T-Lymphocytes / drug effects,  immunology*
Tacrolimus / pharmacology*
Tacrolimus Binding Protein 1A / genetics*,  immunology*,  metabolism
Reg. No./Substance:
0/Antigens, CD28; 0/Antigens, CD3; 0/Immunosuppressive Agents; 109581-93-3/Tacrolimus; 59865-13-3/Cyclosporine; EC 5.2.1.-/Tacrolimus Binding Protein 1A

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