Identification of regulatory T cell molecules associated with severity of multiple sclerosis

Regulatory CD4⁺ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-β is a key regulator of Treg development and function.

The objective of this study is to determine whether the expression of functionally relevant TGF-β-regulated molecules is altered in Tregs from patients with MS.

Expression of nine Treg markers was analyzed by multi-color flow cytometry in CD4⁺ T cells and Treg subpopulations of 31 untreated MS patients and age- and sex-matched healthy donors (HDs). Correlations between Treg marker expression and clinical variables were sought.

Expression of the transcription factor Helios, which defines thymic-derived Tregs, was decreased in this Treg subpopulation. The frequency of peripherally generated Tregs was increased in patients with MS, particularly in patients with progressive MS. Low frequencies of thymic-derived Tregs were associated with magnetic resonance imaging (MRI) lesion-burden and a high relapse rate. Four surface markers associated with TGF-β signaling (ABCA1, BTLA, DNAM-1, and GARP) were differentially expressed on Tregs from patients with MS and HDs. Expression levels of CD73, CD103, ABCA1, and PAR2 showed strong correlations with disease severity.

We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.