Influence of short-term glucocorticoid therapy on regulatory T cells in vivo |
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Authors: | Sbiera Silviu Dexneit Thomas Reichardt Sybille D Michel Kai D van den Brandt Jens Schmull Sebastian Kraus Luitgard Beyer Melanie Mlynski Robert Wortmann Sebastian Allolio Bruno Reichardt Holger M Fassnacht Martin |
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Institution: | Endocrinology and Diabetology Unit, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany. |
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Abstract: | BackgroundPre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs).ObjectiveWe readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naïve mice.MethodsMice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers.ResultsRepeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.8±1.8×104 cells/ml vs. 33±11×104 in control mice) and spleen (dexamethasone: 2.8±1.9×105/spleen vs. 95±22×105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.0±1.5% vs 3.4±1.5%*; AITR+: 0.6±0.4 vs 0.5±0.3%, CD127low: 4.0±1.3 vs 5.0±3.0%* and CTLA4+: 13.8±11.5 vs 15.6±12.5%; * p<0.05).ConclusionShort-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers. |
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