Functional defect in regulatory T cells in myasthenia gravis.

Forkhead box P3 (FOXP3) is a transcription factor necessary for the function of regulatory T cells (Treg cells). Treg cells maintain immune homeostasis and self-tolerance and play an important role in the prevention of autoimmune disease. Here, we discuss the role of Treg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in Treg cell in vitro suppressive function exists in MG patients, without an alteration in circulating frequency. This functional defect is associated with a reduced expression of key functional molecules, such as FOXP3 on isolated Treg cells, and appears to be more pronounced in immunosuppression-naive MG patients. In vitro administration of granulocyte macrophage-colony-stimulating factor (GM-CSF) enhanced the suppressive function of Treg cells and upregulated FOXP3 expression. These findings indicate a clinically relevant Treg cell-intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target. [ABSTRACT FROM AUTHOR]