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...

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Published in:The Journal of immunology (1950) 2009-07, Vol.183 (2), p.841-848
Main Authors: Luther, Claudia, Adamopoulou, Eleni, Stoeckle, Christina, Brucklacher-Waldert, Verena, Rosenkranz, Daniela, Stoltze, Lars, Lauer, Sigrid, Poeschel, Simone, Melms, Arthur, Tolosa, Eva
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Autoimmunity - drug effects
Case-Control Studies
Cell Proliferation
Coculture Techniques
Dendritic Cells - immunology
Humans
Immune Tolerance - drug effects
Interleukins - secretion
Lipopolysaccharides
Middle Aged
Myasthenia Gravis - drug therapy
Myasthenia Gravis - immunology
Prednisolone - pharmacology
Prednisolone - therapeutic use
T-Lymphocytes, Regulatory - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0802046