title: Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients.
abstract: Myasthenia gravis (MG) is an autoimmune disorder generally mediated by antibodies against the acetylcholine receptors (AChR) of the skeletal muscles. CD4 T cells help B cells to produce antibodies through their production of cytokines or chemokines. In this study, we evaluated the frequency of regulatory (Treg) and IL-17 producing CD4 T-cell subsets (Th17) in peripheral blood mononuclear cells (PBMCs) of patients with MG. The transcription factor, forkhead transcription factor (Foxp3), is essential for T-cell regulatory function, and the orphan nuclear receptor, RORgammaT, is important in Th17 cell differentiation. In MG patients, Foxp3 mRNA expression in PBMCs was lower than those in healthy subjects (p=0.007), while there was no significant difference of RORgammaT mRNA expression between MG patients and healthy subjects. Glucocorticoid-induced tumour-necrosis-factor receptor-related protein (GITR) is expressed predominantly on CD4(+)CD25(+) Treg cells. We found that the number of GITR(+)CD4(+)CD25(+) T cells in peripheral lymphocytes in MG patients was lower than that in healthy subjects (P<0.01). In addition, there was a significant positive correlation between the change of the frequency of GITR(+)CD4(+)CD25(+) T cells and the changing rate in quantitative myasthenia gravis scores (%) (p=0.03). Furthermore, there was a significant negative correlation between the change of the percentage of GITR(+)CD4(+)CD25(+) T cells (% lymphocytes) and the changing rate of daily PSL doses (%) (P=0.002). The relative RORgammaT levels in PBMCs negatively correlated with the Th1/Th2 ratio in CD4(+) cells in MG patients (p=0.014). In conclusion, our findings suggest that Th17 cells affect the production of autoantibodies through their influence on the Th1- and Th2-cytokine balance in PBMCs of MG patients. On the other hand, Treg cells are suggested to be involved in the clinical condition or severity of MG disease.
authors.affiliation: Third Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Masuda
authors.forename: Moe
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakajima
authors.forename: Nao
authors.initials: N
authors.lastname: Yamada
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ido
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Masashi
authors.initials: M
authors.lastname: Nishida
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Hiroya
authors.initials: H
authors.lastname: Utsumi
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit