ABSTRACT
BACKGROUND: Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-ß is a key regulator of Treg development and function. OBJECTIVE: The objective of this study is to determine whether the expression of functionally relevant TGF-ß-regulated molecules is altered in Tregs from patients with MS. METHODS: 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. RESULTS: 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-ß 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. CONCLUSION: We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.
Subject(s)
Multiple Sclerosis , T-Lymphocytes, Regulatory , Cells, Cultured , Flow Cytometry , Gene Expression Regulation , HumansABSTRACT
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Subject(s)
Humans , Male , Aged , Chorea/complications , Dyskinesias/complications , Hyperglycinemia, Nonketotic/complications , Visual Cortex/physiopathologySubject(s)
Adenocarcinoma/complications , Brain Diseases/etiology , Cerebral Infarction/etiology , Hypereosinophilic Syndrome/etiology , Paraneoplastic Syndromes/etiology , Prostatic Neoplasms/complications , Adenocarcinoma/diagnosis , Aged , Brain Diseases/pathology , Cerebral Infarction/pathology , Humans , Hypereosinophilic Syndrome/pathology , Magnetic Resonance Imaging , Male , Neoplasms, Unknown Primary/complications , Neoplasms, Unknown Primary/diagnosis , Paraneoplastic Syndromes/pathology , Prostatic Neoplasms/diagnosisABSTRACT
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