Impaired regulatory function in circulating CD4+CD25highCD127low/− T cells in patients with myasthenia gravis

Previous studies have reported alterations in numbers or function of regulatory T (Treg) cells in myasthenia gravis (MG) patients, but published results have been inconsistent, likely due to the isolation of heterogenous “Treg” populations. In this study, we used surface CD4, CD25high, and CD127low/− expression to isolate a relatively pure population of Tregs, and established that there was no alteration in the relative numbers of Tregs within the peripheral T cell pool in MG patients. In vitro proliferation assays, however, demonstrated that Treg-mediated suppression of responder T (Tresp) cells was impaired in MG patients and was associated with a reduced expression of FOXP3 in isolated Tregs. Suppression of both polyclonal and AChR-activated Tresp cells from MG patients could be restored using Tregs isolated from healthy controls, indicating that the defect in immune regulation in MG is primarily localized to isolated Treg cells, and revealing a potential novel therapeutic target.

► CD4+CD25highCD127low Tregs from MG patients have an impaired function.
► Isolated Tregs from MG patients express reduced levels of FOXP3.
► CD4+CD25highCD127low Tregs from controls restore normal suppression of MG T cells.
► The Treg defect is more prominent in immunosuppression-naïve MG patients.