Immunosuppressive drugs affect induction of IFNy+ Treg in vitro

• Verfasst von: Daniel, Volker [VerfasserIn]
• Verfasst von: Trojan, Karina [VerfasserIn]
• Verfasst von: Opelz, Gerhard [VerfasserIn]
• Titel: Immunosuppressive drugs affect induction of IFNy+ Treg in vitro
• Verf.angabe: Volker Daniel, Karina Trojan, Gerhard Opelz
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 7 S.
• Fussnoten: Available online 14 November 2015 ; Gesehen am 06.05.2020
• Titel Quelle: Enthalten in: Human immunology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1980
• Jahr Quelle: 2016
• Band/Heft Quelle: 77(2016), 1, Seite 146-152
• ISSN Quelle: 1879-1166
• DOI: doi:10.1016/j.humimm.2015.11.006
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: IFNy+ Treg
• Sach-SW: Immunosuppression
• Sach-SW: Immunosuppressive drugs
• Sach-SW: Induced Treg
• Sach-SW: Natural Treg
• Sach-SW: Tbet+ Treg
• Sach-SW: Th1-like Treg
• K10plus-PPN: 1697299652

Abstract

Background - We reported previously that patients with poor long-term graft function are able to form IFNy+ Treg in vitro pretransplant, but late posttransplant have more frequently undetectable or lower levels of IFNy+ Treg in the peripheral blood than patients with good long-term graft outcome. In the present study, we investigated the induction of IFNy+ and Tbet+ Treg subsets in the presence of immunosuppressants in vitro. - Methods - PBL of 10 healthy individuals were stimulated with PMA/Ionomycin in the presence of different immunosuppressive drugs at 2 different concentrations that were chosen to approximately mirror the blood levels in renal transplant recipients. IFNy+, Tbet+, CD119+, and Helios+ CD4+CD25+CD127−Foxp3+ Treg subsets were analyzed using 8-color-fluorescence-flow-cytometry. - Results - Cyclosporine (p<0.01) and 6α-methylprednisolone (p<0.05) at both concentrations as well as high doses of azathioprine (p<0.05) and mycophenolate mofetil (p<0.05) inhibited the induction of IFNy+ and Tbet+ Treg, whereas lower concentrations of azathioprine and mycophenolate mofetil tended to increase IFNy+, Tbet+ and CD119+ Treg (p⩽0.05). - Conclusions - Drug-induced inhibition of Treg induction might result in low IFNy+ Treg levels with the consequence of T effector activation and impaired graft function. Further studies will show whether monitoring of IFNy+ Treg might help to prevent clinical complications provoked by an inappropriate immunosuppressive protocol.