title: Functional defect in regulatory T cells in myasthenia gravis.
abstract: 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.
authors.affiliation: Department of Neurology and Rehabilitation, College of Medicine, University of Illinois Hospital and Health Sciences System, Chicago, USA.
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Thiruppathi
authors.forename: Julie
authors.initials: J
authors.lastname: Rowin
authors.forename: Qin
authors.initials: Q
authors.lastname: Li Jiang
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Meriggioli
mesh_terms: D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D009157:Myasthenia Gravis / Q000276:immunology / Q000378:metabolism*; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor