کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3349552 | 1216356 | 2016 | 7 صفحه PDF | دانلود رایگان |
BackgroundWe 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.MethodsPBL 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.ResultsCyclosporine (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).ConclusionsDrug-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.
Journal: Human Immunology - Volume 77, Issue 1, January 2016, Pages 146–152