14082
2011
eng
e24345
9
6
article
1
2016-11-25
--
--
Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells \(In\) \(Vivo\)
Background:
Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(T(reg)) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs).
Objective:
We readdressed the influence of GC therapy on T(reg) cells in immunocompetent human subjects and naive mice.
Methods:
Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and T(reg) 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 T(reg) cells were analyzed prior and after a 14 day GC therapy based on different markers.
Results:
Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of T(reg) cells in blood (100 mg dexamethasone/kg body weight: 2.8 +/- 1.8 x 10(4) cells/ml vs. 33 +/- 11 x 10(4) in control mice) and spleen (dexamethasone: 2.8 +/- 1.9 x 10(5)/spleen vs. 95 +/- 22 x 10(5)/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3(+) T(reg) 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 T(reg) 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 T(reg) cells in a relevant manner, although there was some variation depending on the definition of the T(reg) cells (FOXP3(+): 4.0 +/- 1.5% vs 3.4 +/- 1.5%*; AITR(+): 0.660.4 vs 0.5 +/- 0.3%, CD127(low): 4.0 +/- 1.3 vs 5.0 +/- 3.0%* and CTLA4+: 13.8 +/- 11.5 vs 15.6 +/- 12.5%; * p < 0.05).
Conclusion:
Short-term GC therapy does not induce the hitherto supposed increase in circulating T(reg) cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating T(reg) cell numbers.
PLoS One
10.1371/journal.pone.0024345
urn:nbn:de:bvb:20-opus-140822
PLoS ONE 6(9): e24345. doi:10.1371/journal.pone.0024345
Silviu Sbiera
Thomas Dexneit
Sybille D. Reichardt
Kai D. Michel
Jens van den Brandt
Sebastian Schmull
Luitgard Kraus
Melanie Beyer
Robert Mlynski
Sebastian Wortmann
Bruno Allolio
Holger M. Reichardt
Martin Fassnacht
eng
uncontrolled
Systemic-Lupus-Erythematosus
eng
uncontrolled
Immunological Self-Tolerance
eng
uncontrolled
Multiple-Sclerosis
eng
uncontrolled
Suppressive Function
eng
uncontrolled
Autoimmune-Diseases
eng
uncontrolled
FoxP3 Expression
eng
uncontrolled
Dendritic Cells
eng
uncontrolled
Immune-System
eng
uncontrolled
Sex-Hormones
eng
uncontrolled
Antigen 4
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14082/075_Sbiera_PLOS-ONE.PDF
6350
2011
eng
article
1
2013-01-11
--
--
Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo
Background: Pre- 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). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naı¨ve mice. Methods: Mice 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. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/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+: 4.061.5% vs 3.461.5%*; AITR+: 0.660.4 vs 0.560.3%, CD127low: 4.061.3 vs 5.063.0%* and CTLA4+: 13.8611.5 vs 15.6612.5%; * p,0.05). Conclusion: Short-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.
urn:nbn:de:bvb:20-opus-74749
7474
In: PLOS ONE (2011) 6:9, 10.1371/journal.pone.0024345
Martin Fassnacht
Silviu Sbiera
Thomas Dexneit
Sybille D. Reichardt
Kai D. Michel
Jens van den Brandt
Sebastian Schmull
Luitgard Kraus
Melanie Beyer
Robert Mlynski
Sebastian Wortmann
Bruno Allolio
Holger M. Reichardt
deu
swd
Medizin
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6350/Fassnacht_journal.pone.0024345.pdf