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Prednisolone Treatment Induces Tolerogenic Dendritic Cells and a Regulatory Milieu in Myasthenia Gravis Patients

Claudia Luther^*, Eleni Adamopoulou, Christina Stoeckle^*, Verena Brucklacher-Waldert, Daniela Rosenkranz^*, Lars Stoltze^*, Sigrid Lauer^*, Simone Poeschel^*, Arthur Melms^* and Eva Tolosa^*

^*Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, Tübingen University Hospital, Germany; and Medical Clinic and Policlinic II, Julius-Maximilian University of Würzburg, Germany

FOXP3-expressing naturally occurring CD4⁺CD25^high T regulatory cells (Treg) are relevant in the control of autoimmunity, and a defect in this cell population has been observed in several human autoimmune diseases. We hypothesized that altered functions of peripheral Treg cells might play a role in the immunopathogenesis of myasthenia gravis, a T cell-dependent autoimmune disease characterized by the presence of pathogenic autoantibodies specific for the nicotinic acetylcholine receptor. We report in this study a significant decrease in the in vitro suppressive function of peripheral Treg cells isolated from myasthenia patients in comparison to those from healthy donors. Interestingly, Treg cells from prednisolone-treated myasthenia gravis patients showed an improved suppressive function compared with untreated patients, suggesting that prednisolone may play a role in the control of the peripheral regulatory network. Indeed, prednisolone treatment prevents LPS-induced maturation of monocyte-derived dendritic cells by hampering the up-regulation of costimulatory molecules and by limiting secretion of IL-12 and IL-23, and enhancing IL-10. In addition, CD4⁺ T cells cultured in the presence of such tolerogenic dendritic cells are hyporesponsive and can suppress autologous CD4⁺ T cell proliferation. The results shown in this study indicate that prednisolone treatment promotes an environment that favors immune regulation rather than inflammation.

Address correspondence and reprint requests to Drs. Claudia Luther and Eva Tolosa, Terry Fox Laboratory, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, Canada. E-mail addresses: cluther{at}bccrc.ca and eva.tolosa{at}zmnh.uni-hamburg.de