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.
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-deficientmice, 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: Biagio De Angelis; Gianpietro Dotti; Concetta Quintarelli; Leslie E Huye; Lan Zhang; Ming Zhang; Fabrizio Pane; Helen E Heslop; Malcolm K Brenner; Cliona M Rooney; Barbara Savoldo Journal: Blood Date: 2009-09-16 Impact factor: 22.113
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