Kinetics of IL-6 production defines T effector cell responsiveness to regulatory T cells in multiple sclerosis.

ABSTRACT: In multiple sclerosis (MS) autoaggressive T effector cells (Teff) are not efficiently controlled by regulatory T cells (Treg) but the underlying mechanisms are incompletely understood. Proinflammatory cytokines are key factors facilitating Teff activity in chronic inflammation. Here we investigated the influence of IL-6 on Treg sensitivity of Teff from therapy-naïve MS patients with or without active disease. Compared to healthy volunteers and independent of disease course CD4(+) and especially CD8(+) MS-Teff were insensitive against functional active Treg from healthy controls. This unresponsiveness was caused by accelerated production of IL-6, elevated IL-6 receptor expression and phosphorylation of protein kinase B (PKB)/c-Akt in MS-Teff. In a positive feedback loop, IL-6 itself induced

SUBMITTER: Trinschek B 

PROVIDER: S-EPMC3796502 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature