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 (T-reg cells). T-reg cells maintain immune homeostasis and self-tolerance and play an important role in the prevention of autoimmune disease. Here, we discuss the role of T-reg cells in the pathogenesis of myasthenia gravis (MG) and review evidence indicating that a significant defect in T-reg 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 T-reg 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 T-reg cells and upregulated FOXP3 expression. These findings indicate a clinically relevant T-reg cell-intrinsic defect in immune regulation in MG that may reveal a novel therapeutic target.