Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients.

Abstract

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.

• Authors: Claudia Luther, Eleni Adamopoulou, Christina Stoeckle, Verena Brucklacher-Waldert, Daniela Rosenkranz, Lars Stoltze, Sigrid Lauer, Simone Poeschel, Arthur Melms, Eva Tolosa
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 183 Issue 2 Pg. 841-8 (Jul 15 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19542375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukins
• Lipopolysaccharides
• Prednisolone

Topics

• 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 (metabolism)
• Lipopolysaccharides
• Middle Aged
• Myasthenia Gravis (drug therapy, immunology)
• Prednisolone (pharmacology, therapeutic use)
• T-Lymphocytes, Regulatory (immunology)