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, RORγT, 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 RORγT 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 RORγT 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.