Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients.
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.
Luther
Claudia
C
Department of General Neurology and Neurodegenerative Disorders, Hertie Institute for Clinical Brain Research, Tübingen University Hospital, Germany. cluther@bccrc.ca
Adamopoulou
Eleni
E
Stoeckle
Christina
C
Brucklacher-Waldert
Verena
V
Rosenkranz
Daniela
D
Stoltze
Lars
L
Lauer
Sigrid
S
Poeschel
Simone
S
Melms
Arthur
A
Tolosa
Eva
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015551:Autoimmunity / Q000187:drug effects; D016022:Case-Control Studies; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000276:immunology; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007378:Interleukins; D008070:Lipopolysaccharides; D011239:Prednisolone