Immunosuppressive drugs affect induction of IFNy+ Treg in vitro
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...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2016
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| In: |
Human immunology
Year: 2015, Volume: 77, Issue: 1, Pages: 146-152 |
| ISSN: | 1879-1166 |
| DOI: | 10.1016/j.humimm.2015.11.006 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.humimm.2015.11.006 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0198885915005595 
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| Author Notes: | Volker Daniel, Karina Trojan, Gerhard Opelz |
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| 520 | |a 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. | ||
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