title: Monotherapy rapamycin allows an increase of CD4 CD25 FoxP3 T cells in renal recipients.
abstract: CD4(+) CD25(bright+) FoxP3(+) regulatory T cells (Tregs) may control donor-specific allogeneic responses in kidney transplant recipients. Recent evidence demonstrated that three phenotypical Treg-subsets, naive (CCR7(+)CD45RO(-)), central-memory (CCR7(+)CD45RO(+)) and effector-memory (CCR7(-)CD45RO(+)), are essential for the development and function of antigen-specific suppression in the lymphoid and peripheral tissues. Also, it has been appreciated that Tregs are affected by immunosuppressive agents. In clinical practice, however, the effect of a single drug remains to be determined. Therefore, we analyzed the effect of several immunosuppressive agents on the number, phenotype and function of peripheral Tregs from 46 stable kidney transplant recipients. These patients were converted to monotherapy with tacrolimus (n = 15), rapamycin (n = 17) or mycophenolate mofetil (n = 14). Blood was obtained at inclusion and 6 months thereafter. The number of Tregs increased significantly in patients on monotherapy with rapamycin (P < 0.001), which was caused by increased numbers of Tregs with a central-memory and an effector-memory phenotype (both P < 0.05). At 6 months after conversion, however, the suppressive function of Tregs did not significantly change in co-cultures stimulated with donor-Ag. Therefore, monotherapy with rapamycin allows the signals that are needed to increase the number of functional Tregs with a memory phenotype, thereby enhancing the potential capacity to regulate donor-specific responses in the lymphoid and the peripheral tissues.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Thijs K
authors.initials: TK
authors.lastname: Hendrikx
authors.forename: Jurjen H L
authors.initials: JH
authors.lastname: Velthuis
authors.forename: Mariska
authors.initials: M
authors.lastname: Klepper
authors.forename: Eveline
authors.initials: E
authors.lastname: van Gurp
authors.forename: Annemarie
authors.initials: A
authors.lastname: Geel
authors.forename: Wenda
authors.initials: W
authors.lastname: Schoordijk
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus