Influence of short-term glucocorticoid therapy on regulatory T cells
Thomas Dexneit1, Silviu Sbiera1, Sebastian Schmull1, Jens van den Brandt2, Luitgart Kraus1, Melanie Beyer1, Robert Mlynski1, Holger Reichardt1, Bruno Allolio1 & Martin Fassnacht1
Introduction: Glucocorticoids (GC) are used for immunosuppression in many clinical conditions. Pre-clinical and early clinical studies suggested that the induction of regulatory T (Treg) cells contributes to the immunosupressive effects of GCs. However, in the hitherto reported clinical studies only patients with ongoing autoimmune diseases were included. Our goal, therefore, was to determine the influence of exogenous GCs in vivo in immunocompetent subjects and mice.
Methods: Sixteen otherwise healthy patients with sudden hearing loss that were treated with GCs (modified Stennert scheme: day 13: 250 mg prednisolone i.v., day 414 dose reduction to 10 mg prednisolone p.o.) were included. Circulating Treg cells, defined as CD4+ CD25 high FoxP3+, were characterized on day 0 and 14 of GC administration using FACS analysis. In addition, Balb/c mice were treated with dexamethasone (day 13: 100 mg/kg i.p., day 414 dose reduction to 1 mg/l p.o.) to further evaluate the effects of very high dose GCs, comparable to the dosage e.g. used in multiple sclerosis.
Results: In contrast to our expectations, GCs induced an increase of lymphocytes in our subjects (mean T cells before and after GCs 1503 vs 2327/μl (P<0.001) without any relevant change of the relative frequency of T cell subpopulations (e.g. CD4+ cells 75.5 vs 75.7%). The percentage of Treg cells even slightly dropped (4.2 vs 3.4%; P=0.02).
In mice, GCs led to a strong decrease of CD4+ T cells in blood (3.7*105 to 0.8*105/ml) and spleen (1.5*107 to 0.3*107/ml) after 14 days. Accordingly the absolute number of Treg cells was also significantly reduced. However, relative frequency of Treg cells amongst all CD4+ T cells remained unchanged in spleen (8.0 vs 7.5%) and decreased in peripheral blood (7.5 vs 1.75%; P<0.01).
Conclusion: Neither in immunocompetent humans nor in mice short-term GC therapy induced the supposed increase of circulating Treg cells. Thus, it is doubtful whether GCs act via influencing Treg cells.