title: Fatigue is not associated with impaired function of regulatory T cells in untreated patients with multiple sclerosis.
abstract: BACKGROUND
  The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients.
  
  
  METHODS
  In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls.
  
  
  RESULTS
  Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25- cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity.
  
  
  CONCLUSIONS
  Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.
authors.affiliation: Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland. yaldizli@gmx.net
authors.forename: Ozguer
authors.initials: O
authors.lastname: Yaldizli
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Susanne
authors.initials: S
authors.lastname: Vago
authors.forename: Erich
authors.initials: E
authors.lastname: Kreuzfelder
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
authors.forename: Norman
authors.initials: N
authors.lastname: Putzki
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D005221:Fatigue / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D051858:Forkhead Transcription Factors; D012333:RNA, Messenger