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

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

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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.

Original languageEnglish
Pages (from-to)1835-1838
Number of pages4
JournalTransplantation
Volume73
Issue number11
StatePublished - Jun 15 2002

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Tacrolimus Binding Protein 1A
Tacrolimus Binding Proteins
Tacrolimus
Immunosuppressive Agents
T-Lymphocytes
Immunophilins
Sirolimus
Growth
Immunosuppression
Inhibition (Psychology)
tacrolimus binding protein 1B
Pharmacology
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506. / Xu, Xuehong; Su, Bing; Barndt, Robert J.; Chen, Hanying; Xin, Hongbo; Yan, Guifan; Chen, Linyuan; Cheng, Dongsheng; Heitman, Joseph; Zhuang, Yuan; Fleischer, Sidney; Shou, Weinian.

In: Transplantation, Vol. 73, No. 11, 15.06.2002, p. 1835-1838.

Research output: Contribution to journalArticle

Xu, X, Su, B, Barndt, RJ, Chen, H, Xin, H, Yan, G, Chen, L, Cheng, D, Heitman, J, Zhuang, Y, Fleischer, S & Shou, W 2002, 'FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506', Transplantation, vol. 73, no. 11, pp. 1835-1838.
Xu, Xuehong ; Su, Bing ; Barndt, Robert J. ; Chen, Hanying ; Xin, Hongbo ; Yan, Guifan ; Chen, Linyuan ; Cheng, Dongsheng ; Heitman, Joseph ; Zhuang, Yuan ; Fleischer, Sidney ; Shou, Weinian. / FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506. In: Transplantation. 2002 ; Vol. 73, No. 11. pp. 1835-1838.
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AU - Xu, Xuehong

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AU - Barndt, Robert J.

AU - Chen, Hanying

AU - Xin, Hongbo

AU - Yan, Guifan

AU - Chen, Linyuan

AU - Cheng, Dongsheng

AU - Heitman, Joseph

AU - Zhuang, Yuan

AU - Fleischer, Sidney

AU - Shou, Weinian

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N2 - 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.

AB - 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.

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