Compromised CD4+ CD25high regulatory T‐cell function in patients with relapsing‐remitting multiple sclerosis is correlated with a reduced frequency of FOXP3‐positive cells and reduced FOXP3 expression at the single‐cell level

Abstract

Compromised CD4+ CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level Introduction CD4+ CD25+ regulatory T cells are a subpopulation of suppressor T cells that play an important role in down- modulating the activation and effector function of poten- tial auto-aggressive T cells.1,2 Loss of Tregs in animal models has demonstrated their importance in maintaining self tolerance, as these animals develop a variety of auto- immune manifestations. The interleukin (IL)-2 receptor a-chain (CD25), a marker commonly used to quantify Tregs, is not sufficiently specific as it is also expressed by activated T cells. Measurement of FOXP3 expression on T cells isolated directly ex vivo allows a more accurate inves- tigation of the Treg frequency in healthy individuals and patients with immune disorders. The gene encoding the transcription factor FOXP3 was discovered as a master gene in the development of Tregs of mice.3,4 Loss- of-function mutations in the FOXP3 gene lead to the development of a severe lymphoproliferative disease and autoimmune manifestations in mice (scurfy model) and in patients with the immuno-dysregulatory, polyendocrino- pathy, enteritis X-linked (IPEX) syndrome.5 We and others have reported that Tregs are functionally impaired in patients with relapsing-remitting (RR) multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS).6–8 In contrast, patients with Koen Venken,1 Niels Hellings,1 Marielle Thewissen,1 Veerle Somers,1 Karen Hensen,2 Jean-Luc Rummens,2 Robert Medaer,1 Raymond Hupperts3 and Piet Stinissen1 1Hasselt University, Biomedisch Onder- zoeksinstituut and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium, 2Clinical Laboratory of Experimental Hematology, Virga Jesse Hospital, Hasselt, Belgium, and 3Department of Neurology, University Hospita

Key Biomarkers

Symptom Clusters